Effects of topical prostaglandin therapy on corneal layers thickness in primary open-angle glaucoma patients using anterior segment optical coherence tomography.

PURPOSE: To evaluate the effects of latanoprost, bimatoprost, and travoprost eye drops and their preservatives on each corneal layer thickness in patients with primary open-angle glaucoma (POAG). METHODS: We retrospectively analyzed 79 eyes of 79 patients with POAG who were receiving prostaglandin therapy. Patients were divided into three subgroups according to monotherapy with latanoprost, bimatoprost, and travoprost during a mean of 43.14 ± 19.12 months follow-up period. In addition, the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) were measured by anterior segment optical coherence tomography (AS-OCT) at baseline and every six months after treatment initiation at each visit between 9 and 12 o'clock in the morning. Furthermore, intraocular pressure (IOP) was measured with Goldmann applanation tonometry (GAT) after AS-OCT measurements at each visit. RESULTS: All three groups were not significantly different in age, gender, follow-up period, and mean intraocular pressure values (p > 0.05 for all). The reduction of CCT in the latanoprost, bimatoprost, and travoprost groups was 6.53 ± 3.17, 18.59 ± 8.42, and 10.1 ± 1.13 µm, respectively. The decrease in CST values was 4.65 ± 1.54, 15.84 ± 7.47, 9.69 ± 1.45 µm, and CET values were 1.88 ± 1.66, 2.75 ± 0.73, 0.41 ± 0.54 µm in all groups, respectively. A statistically significant thinning was observed in all corneal layers (p < 0.05) except the CST values in the latanoprost group and CET values in the travoprost group. However, no significant difference was found in the average reduction of CET, CST, and CCT values among the three groups (p > 0.05). CONCLUSION: Topical treatment with latanoprost, bimatoprost, and travoprost affects each layer of the cornea separately according to the active and protective substances contained in these eye drops. On the other hand, the thinning effect on the corneal layers was similar in these three drugs because there was no significant difference between the three groups in the total amount of thinning of the corneal layers during the follow-up period.

MOLECULAR PATHWAYS IN THE ENDOCRINOLOGY OF PARTURITION.

The entire complex process of labor is the central concern of obstetrics and premature labor poses a threat to the mother and fetus and represents a core medical and social issue. In this respect, understanding the mechanism of uterine contractions at a molecular level helps shed some light on possible future prevention and treatment. New research has emphasized the role of endocannabinoids by two metabolic pathways with final products that act as antagonists: prostaglandins and prostamides (prostaglandin-ethanolamides), but with competition on substrates and enzymes. Thus, the dominant pathway will be selected on account of cellular and tissue environment.

Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator.

Recently, endocannabinoids have emerged as signalling mediators in reproduction. It is widely accepted that anandamide (AEA) levels must be tightly regulated, and that a disturbance in AEA levels may impact decidual stability and regression. We have previously characterized the endocannabinoid machinery in rat decidual tissue and reported the pro-apoptotic action of AEA on rat decidual cells. Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays a crucial role in early pregnancy, and is also a key modulator in the crosstalk between endocannabinoids and prostaglandins. On the other hand, AEA-oxidative metabolism by COX-2 is not merely a mean to inactivate its action, but it yields the formation of a new class of mediators, named prostaglandin-ethanolamides, or prostamides. In this study we found that AEA-induced apoptosis in decidual cells involves COX-2 metabolic pathway. AEA induced COX-2 expression through p38 MAPK, resulting in the formation of prostamide E2 (PME2). Our findings also suggest that AEA-induced effect is associated with NF-kB activation. Finally, we describe the involvement of PME2 in the induction of the intrinsic apoptotic pathway in rat decidual cells. Altogether, our findings highlight the role of COX-2 as a gatekeeper in the uterine environment and clarify the impact of the deregulation of AEA levels on the decidual remodelling process.

Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases.

The naturally occurring mammalian endocannabinoids possess biological attributes that extend beyond interaction with cannabinoid receptors. These extended biological properties are the result of oxidative metabolism of the principal mammalian endocannabinoids arachidonoyl ethanolamide (anandamide; A-EA) and 2-arachidonoylglycerol (2-AG). Both endocannabinoids are oxidized by cyclo-oxygenase-2 (COX-2), but not by COX-1, to a series of prostaglandin derivatives (PGs) with quite different biological properties from those of the parent substrates. PG ethanolamides (prostamides, PG-EAs) and PG glyceryl esters (PG-Gs) are not only pharmacologically distinct from their parent endocannabinoids, they are distinct from the corresponding acidic PGs, and are differentiated from each other. Ethanolamides and glyceryl esters of the major prostanoids PGD2, PGE2, PGF2α, and PGI2 are formed by the various PG synthases, and thromboxane ethanolamides and glyceryl esters are not similarly produced. COX-2 is also of interest by virtue of its corollary central role in modulating endocannabinoid tone, providing a new therapeutic approach for treating pain and anxiety. Other major oxidative conversion pathways are provided for both A-EA and 2-AG by several lipoxygenases (LOXs), resulting in the formation of numerous hydroxyl metabolites. These do not necessarily represent inactivation pathways for endocannabinoids but may mimic or modulate the endocannabinoids or even display alternative pharmacology. Similarly, A-EA and 2-AG may be oxidized by P450 enzymes. Again a very diverse number of metabolites are formed, with either cannabinoid-like biological properties or an introduction of disparate pharmacology. The biological activity of epoxy and hydroxyl derivatives of the endocannabinoids remains to be fully elucidated. This review attempts to consolidate and compare the findings obtained to date in an increasingly important research area. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

Tolerability and efficacy of bimatoprost 0.01 % in patients with open-angle glaucoma or ocular hypertension evaluated in the Taiwanese clinical setting: the Asia Pacific Patterns from Early Access of Lumigan 0.01 % (APPEAL Taiwan) study.

BACKGROUND: In randomized, controlled trials of open-angle glaucoma (OAG) or ocular hypertension (OHT), bimatoprost 0.01 % improved tolerability while retaining the intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.03 %. Given geographic/racial differences in glaucoma presentation, the APPEAL study assessed the occurrence and severity of hyperemia produced by bimatoprost 0.01 %, and its efficacy, in the Taiwanese clinical setting. METHODS: In this multicenter, open-label, observational study, treatment-naïve and previously treated patients with OHT or OAG received once-daily bimatoprost 0.01 % for 12 weeks. Hyperemia (primary endpoint) was graded at baseline, week 6, and week 12 using a photonumeric scale (0, +0.5, +1, +2, +3), grouped (≤ +1, none to mild; ≥ +2, moderate to severe), and reported as unchanged from baseline, improved, or worsened. IOP assessments followed the same schedule. Supplemental efficacy analyses were conducted based on previous therapies. RESULTS: The intent-to-treat population (N = 312) included treatment-naïve (13.5 %) and previously treated (86.5 %) patients; mean age was 53.3 years. At baseline, 46.3 % of previously treated patients were receiving prostaglandin analog (PGA) monotherapy. At week 12, 91.2 %, 5.9 %, and 2.9 % of treatment-naïve patients exhibited unchanged, worsened, and improved hyperemia from baseline, respectively; 77.9 %, 12.9 %, and 9.2 % of previously treated patients showed no change, worsening, and improvement, respectively. There were no statistically significant shifts in hyperemia severity in either group, or in subgroups based on previous use of any PGA, any non-PGA, latanoprost, or travoprost monotherapies. In treatment-naïve patients, mean IOP reduction from baseline (18.0 ± 3.8 mm Hg) was 3.6 mm Hg at week 12 (P < 0.0001); 83.3 % had baseline IOP ≤ 21 mm Hg. In previously treated patients, mean additional IOP reduction from baseline (17.8 ± 3.9 mm Hg) was 2.6 mm Hg (P < 0.0001); similar results were observed in patient subgroups based on previous therapies. CONCLUSIONS: In the Taiwanese clinical setting, bimatoprost 0.01 % provided significant IOP lowering in treatment-naïve patients (regardless of baseline IOP) and previously treated patients (even those with relatively low IOP on other therapies), while causing no significant changes in hyperemia from baseline. TRIAL REGISTRATION: Clinicaltrials.gov NCT01814761 . Registered 18 March 2013.

Anandamide-derived prostamide F2α negatively regulates adipogenesis.

Lipid mediators variedly affect adipocyte differentiation. Anandamide stimulates adipogenesis via CB1 receptors and peroxisome proliferator-activated receptor γ. Anandamide may be converted by PTGS2 (COX2) and prostaglandin F synthases, such as prostamide/prostaglandin F synthase, to prostaglandin F2α ethanolamide (PGF2αEA), of which bimatoprost is a potent synthetic analog. PGF2αEA/bimatoprost act via prostaglandin F2αFP receptor/FP alt4 splicing variant heterodimers. We investigated whether prostamide signaling occurs in preadipocytes and controls adipogenesis. Exposure of mouse 3T3-L1 or human preadipocytes to PGF2αEA/bimatoprost during early differentiation inhibits adipogenesis. PGF2αEA is produced from anandamide in preadipocytes and much less so in differentiating adipocytes, which express much less PTGS2, FP, and its alt4 splicing variant. Selective antagonism of PGF2αEA receptors counteracts prostamide effects on adipogenesis, as does inhibition of ERK1/2 phosphorylation. Selective inhibition of PGF2αEA versus prostaglandin F2α biosynthesis accelerates adipogenesis. PGF2αEA levels are reduced in the white adipose tissue of high fat diet-fed mice where there is a high requirement for new adipocytes. Prostamides also inhibit zebrafish larval adipogenesis in vivo. We propose that prostamide signaling in preadipocytes is a novel anandamide-derived antiadipogenic mechanism.

Bimatoprost promotes satiety and attenuates body weight gain in rats fed standard or obesity-promoting diets.

Bimatoprost is a synthetic prostamide F2α analog that down-regulates adipogenesis in vitro. This effect has been attributed to participation in a negative feedback loop that regulates anandamide-induced adipogenesis. A follow-on investigation has now been conducted into the broader metabolic effects of bimatoprost using rats under both normal state and obesity-inducing conditions. Chronic bimatoprost administration attenuated weight gain in a dose dependent-manner in rats fed either standard [max effect -7%] or obesity-promoting diets [max effect -23%] over a 9-10 week period. Consistent with these findings, bimatoprost promoted satiety as measured by decreased food intake [max effect, -7%], gastric emptying [max effect, -33-50%] and decreased circulating concentrations of the gut hormones, ghrelin and GLP-1 [max effect, -33-50%]. Additionally, subcutaneous, and visceral fat mass were distinctly affected by treatment [-30% diet independent]. Taken together, these results suggest that bimatoprost regulates energy homeostasis through promoting satiety and a decrease in food intake. These newly reported activities of bimatoprost reveal an additional method of metabolic disease intervention for potential therapeutic exploitation.

Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.

Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo. To assess the chemotherapeutic potential of 15d-PMJ2, the current study sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity. B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death. Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death. PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, we show the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity. The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.

Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure.

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F2α and prostaglandin F2α (PGF2α.). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F2α levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (Fam213b / Prxl2b) was accomplished by a two exon disruption. Prostamide F2α levels in wild type (WT) and PM/PGFS knock-out (KO) mice were determined by LC/MS/MS. Deletion of Fam213b (Prxl2b) had no observed effect on behavior, appetite, or fertility. In contrast, tonometrically measured intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. Outflow facility was measured in enucleated mouse eyes using the iPerfusion system. No effect on pressure dependent outflow facility occurred, which is consistent with the effects of prostamide F2α and PGF2α increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids known to raise intraocular pressure, namely prostaglandin D2 (PGD2) and thromboxane A2 (TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2α and prostamide F2α to constrain the influence of those prostanoids that raise intraocular pressure.

Endocannabinoid and Prostanoid Crosstalk in Pain.

Interfering with endocannabinoid (eCB) metabolism to increase their levels is a proven anti-nociception strategy. However, because the eCB and prostanoid systems are intertwined, interfering with eCB metabolism will affect the prostanoid system and inversely. Key to this connection is the production of the cyclooxygenase (COX) substrate arachidonic acid upon eCB hydrolysis as well as the ability of COX to metabolize the eCBs anandamide (AEA) and 2-arachidonoylglycerol (2-AG) into prostaglandin-ethanolamides (PG-EA) and prostaglandin-glycerol esters (PG-G), respectively. Recent studies shed light on the role of PG-Gs and PG-EAs in nociception and inflammation. Here, we discuss the role of these complex systems in nociception and new opportunities to alleviate pain by interacting with them.

Therapeutic potential of bimatoprost for the treatment of eyebrow hypotrichosis.

Eyebrows serve as a key feature of the face and have many roles, including cosmetic appearance and social communication. Eyebrow hypotrichosis, which refers to reduction or absence of the eyebrow hair, could be a major problem that leads to negative functional, psychological, and social consequences. Bimatoprost is an ophthalmic prostamide analog that is approved by the United States Food and Drug Administration for the treatment of eyelash hypotrichosis. Its proposed mechanism is stimulation of the prostaglandin receptor in dermal papilla and melanocyte, thus leading to a prolonged anagen phase and increased melanogenesis. The hair follicle then increases in thickness, length, and darkness. The efficacy of bimatoprost for the treatment of eyebrow hypotrichosis has been supported by well-controlled studies. Bimatoprost, which is noninvasive, effective, and well tolerated, is worth considering as a treatment option for eyebrow hypotrichosis.

Topical Treatment of Eyebrow Hypotrichosis with Bimatoprost 0.03% Solution: Case Report and Literature Review.

The eyebrows frame the upper margin of the orbit and are an essential feature of the facial landscape. Eyebrow hypotrichosis, also known as madarosis, is characterized by a lack of growth or loss of eyebrow hair. Eyebrow loss can have cosmetic, functional, and social consequences. Eyebrow hypotrichosis can be idiopathic or related to an underlying condition. Bimatoprost 0.03% solution is a prostamide F2α analog indicated for the treatment of glaucoma and ocular hypertension that has also demonstrated efficacy for hair growth; indeed, it is currently approved by the Food and Drug Administration for the treatment of eyelash hypotrichosis. A 60-year-old woman with eyebrow hypotrichosis is described who achieved excellent and sustained growth of her eyebrows with continual daily application of bimatoprost 0.03% solution. We discuss the therapeutic mechanisms of bimatoprost 0.03% solution in hair growth, review other potential modalities for treating eyebrow hypotrichosis, and summarize the findings of investigators who have utilized bimatoprost in the treatment of eyebrow hypotrichosis.

Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain.

Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs.

Prospective, non-interventional, multicenter study of the intraocular pressure-lowering effects of prostaglandin analog/prostamide-containing therapies in previously treated patients with open-angle glaucoma or ocular hypertension.

OBJECTIVE: The objective of this study was to assess the intraocular pressure (IOP)-lowering efficacy, tolerability, safety, and usage patterns of prostaglandin analog/prostamide (PGA/P)-containing topical ocular hypotensives in ocular hypertension (OHT) and primary open-angle glaucoma in the Turkish clinical setting. METHODS: This non-interventional, multicenter study enrolled previously treated patients who failed to achieve target IOP (or experienced unacceptable adverse events [AEs]) and were prescribed a PGA/P-containing IOP-lowering agent. Treatment was initiated at baseline (V1), and patients returned at weeks 4-6 (V2) and 8-12 (V3). The primary efficacy measure was the change in IOP from baseline at V3 in each eye. The secondary measures were physician's assessment of IOP-lowering efficacy, patients (%) reaching target IOP determined at V1, hyperemia score, physician and patient assessment of study treatment tolerability at V3, and AE frequency/severity. A subgroup analysis of patients receiving the most common study treatment was conducted. All analyses were performed using the safety population (patients who received one or more doses and had any data available). RESULTS: Of 358 enrolled patients, 60.6% had primary open-angle glaucoma, 29.9% had secondary open-angle glaucoma (protocol amendment), and 13.1% had OHT; 13 patients had multiple diagnoses. At V3, the mean IOP change from baseline was ≥-4.2 mmHg (≥21.1%). IOP met or was lower than the target in 81.7% of patients, 95% exhibited none to mild conjunctival hyperemia (most common AE), and tolerability was rated good/very good by >91.1% of patients and physicians. The results were similar in patients who received the most common study treatment, bimatoprost 0.03%/timolol 0.5% (bim/tim; n=310). CONCLUSION: PGA/P-containing medications, including bim/tim, significantly reduced IOP in previously treated patients with open-angle glaucoma or OHT; most reached their target IOP or an IOP even lower than their target and reported good/very good tolerability. PGA/P-containing medications such as bim/tim should be considered as a safe, effective therapeutic option for Turkish patients who exhibit poor response, tolerance, or adherence to their previous therapy.

Bimatoprost for the treatment of eyelash, eyebrow and scalp alopecia.

INTRODUCTION: Alopecia is a common condition observed among people of all ages. It is a disorder that can involve only the scalp as observed in androgenetic alopecia or scalp and body as in alopecia areata or patients under chemotherapy treatment. There are several treatment options with different safety and efficacy outcomes. Bimatoprost, a synthetic prostamide F2α analog originally approved for the treatment of ocular hypertension and open-angle glaucoma, is now FDA approved as a 0.03%, solution to be applied once daily to increase eyelashes growth. Areas covered: In this review, the authors evaluate the role of bimatoprost in idiopathic hypotrichosis of the eyelashes, in hypotrichosis of the eyelashes associated to chemotherapy, in alopecia areata of the eyelashes and eyebrows and in androgenetic alopecia. In addition, pharmacokinetics, pharmacodynamics, safety and tolerability of bimatoprost are discussed. Expert opinion: Bimatoprost will likely be the third FDA approved weapon in the fight against hair loss. Prostaglandin analogs are the only possible treatment for hypotrichosis and alopecia of the eyelashes regardless of its etiology. Eyebrow hypotrichosis due to alopecia areata or frontal fibrosis alopecia can also possibly benefit of these medications.

Bimatoprost/timolol fixed combination (BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece.

AIM: To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03% and timolol 0.5% (BTFC) in patients in Greece with primary open angle glaucoma (POAG) or ocular hypertension (OHT) whose previous therapy provided insufficient lowering of intraocular pressure (IOP). METHODS: A multicenter, prospective, open-label, non-interventional, observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece. The primary endpoint was the reduction in IOP from baseline at study end, approximately 12wk after initiation of BTFC therapy. RESULTS: A total of 785 eligible patients were enrolled in the study and 97.6% completed the study. The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg (n=764; P<0.001). In patients (n=680) who replaced their previous IOP-lowering monotherapy (a single drug, or a fixed combination of 2 drugs in a single ophthalmic drop) with once-daily BTFC, the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg (P<0.001). IOP was reduced from baseline in 99.2% of patients, and 58.0% of patients reached or exceeded their target IOP. Substantial mean IOP reductions were observed regardless of the previous therapy. BTFC was well tolerated, with 96.0% of patients who completed the study rating the tolerability of BTFC as "good" or "very good." Adverse events were reported in 8.3% of patients; only 0.6% of patients discontinued the study due to adverse events. CONCLUSION: In clinical practice in Greece, BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

Bimatoprost 0.01 % for previously treated patients with open-angle glaucoma or ocular hypertension in the Korean clinical setting.

PURPOSE: To evaluate the occurrence of hyperemia with, and efficacy of, bimatoprost 0.01 % for patients in Korea previously treated for open-angle glaucoma (OAG; including normal tension glaucoma) or ocular hypertension (OHT). METHODS: In this multicenter, observational study (Asia Pacific Patterns from Early Access of Lumigan 0.01 % in Korea; APPEAL Korea), patients with unachieved target intraocular pressure (IOP) despite previous treatment received bimatoprost 0.01 % daily for 12 weeks. The primary endpoint was incidence of hyperemia and its severity, graded using the standard 5-point photographic scale and grouped as "none to mild" and "moderate to severe". Hyperemia shifts were reported. IOP and adverse events (AEs) were recorded. RESULTS: Of 800 patients (intent-to-treat/safety population), 248 were switched from previous treatment to bimatoprost 0.01 % monotherapy. Hyperemia shifts from baseline at weeks 6 and 12 were unchanged (84.8, 89.8 %), improved (4.4, 4.8 %), or worsened (10.8, 5.4 %), respectively. The shift was significant at week 6 (P < 0.0001). Hyperemia did not worsen significantly in patients previously receiving a prostaglandin analog or prostamide (PGA/PSD). Baseline mean IOP ± SD was 17.0 ± 5.7 mmHg, decreasing to 14.6 ± 3.8 mmHg (P < 0.0001) after 6 weeks, and to 14.7 ± 3.6 mmHg (P < 0.0001) after 12 weeks. Patients switched from PGA or PSD (excluding bimatoprost 0.03 %) to bimatoprost 0.01 % experienced significant IOP reductions from baseline. Treatment-related ocular AEs were reported by 37 patients, the most common being hyperemia (7.3 %). CONCLUSIONS: This subanalysis of the APPEAL Korea study supports use of bimatoprost 0.01 % for previously treated patients with OAG (including normal tension glaucoma) or OHT who did not reach target IOP or were intolerant of previous treatment.

Bimatoprost 0.01% or 0.03% in patients with glaucoma or ocular hypertension previously treated with latanoprost: two randomized 12-week trials.

BACKGROUND: The purpose of this study was to evaluate the intraocular pressure (IOP)-lowering efficacy and safety of bimatoprost 0.01% or 0.03% as monotherapy in patients treated with latanoprost 0.005% monotherapy who require additional IOP lowering for their ocular hypertension or open-angle glaucoma. METHODS: Two prospective, investigator-masked, randomized, parallel-group, multicenter studies enrolled patients with baseline IOP ≥20 mmHg after ≥30 days of latanoprost 0.005% monotherapy. Patients were randomized to 12 weeks of study treatment (study 1, bimatoprost 0.01% once daily or bimatoprost 0.01% once daily plus brimonidine 0.1% three times daily; study 2, bimatoprost 0.03% once daily or bimatoprost 0.03% once daily plus fixed-combination brimonidine 0.2%/timolol 0.5% twice daily). Patient evaluations at weeks 4 and 12 included IOP at 8 am, 10 am, and 4 pm and safety assessments. Results in the monotherapy study arms (bimatoprost 0.01% or 0.03%) are presented. RESULTS: Latanoprost-treated baseline mean diurnal IOP (± standard error of the mean) was 22.2±0.3 mmHg and 22.1±0.4 mmHg in the bimatoprost 0.01% and bimatoprost 0.03% treatment arms, respectively (P=0.957). In both treatment arms, mean (± standard error of the mean) reduction in IOP from latanoprost-treated baseline was statistically significant at each time point at both follow-up visits (P<0.001), ranging from 3.7±0.4 (17.0%) mmHg to 4.4±0.4 (19.9%) mmHg with bimatoprost 0.01% and from 2.8±0.5 (12.8%) mmHg to 3.9±0.5 (16.7%) mmHg with bimatoprost 0.03%. Mean percentage IOP reduction from latanoprost-treated baseline was numerically greater with bimatoprost 0.01% than with bimatoprost 0.03% throughout follow-up. The incidence of conjunctival hyperemia of mild or greater severity increased from latanoprost baseline after 12 weeks of treatment only in the bimatoprost 0.03% treatment arm. CONCLUSION: Many patients who do not reach their target IOP on latanoprost can achieve additional IOP lowering and maintain monotherapy by replacing latanoprost with bimatoprost. Reductions in IOP from latanoprost baseline were larger with bimatoprost 0.01% than with bimatoprost 0.03%, and bimatoprost 0.01% had a more favorable tolerability profile.

Paired-eye comparison of medical therapies for glaucoma.

OBJECTIVE: To evaluate efficacy and patient preference retrospectively among intraocular pressure (IOP)-lowering prostamide and prostaglandin medications in a real-world clinical setting. METHODS: Chart review of patients with uncontrolled glaucoma or ocular hypertension seen at a private practice clinic (n = 55) who received bimatoprost 0.03% once daily in one eye and either travoprost 0.004% or latanoprost 0.005% once daily in the fellow eye. IOP was evaluated at the initial visit and at a follow-up visit scheduled 4-6 weeks later. At the follow-up visit, each patient discussed the clinical results with their physician, chose which medication they preferred to continue using, and were queried regarding the reason for their choice. This paired-eye comparison method is used routinely in clinical practice to assess clinical response and involve patients in decisions regarding treatment. Change in mean IOP from baseline and patient medication choice were the outcome measures. RESULTS: Bimatoprost-treated eyes (n = 52) had a mean IOP reduction of 2.7 mmHg and travoprost-treated eyes (n = 47) had an average decrease of 1.7 mmHg (P = 0.230). Bimatoprost significantly reduced mean IOP (from 19.8 mmHg at baseline to 17.1 mmHg at follow-up, P < 0.0001), as did travoprost (from 19.4 mmHg at baseline to 17.7 mmHg at follow-up, P = 0.009). Latanoprost-treated eyes were excluded from the efficacy analysis due to small sample size (n = 5). For continued therapy, patients chose bimatoprost over travoprost by a factor of 2.4 to 1. Of the 15 patients who gave a reason for their choice, 80% said their decision was based primarily on IOP change. CONCLUSIONS: Bimatoprost and travoprost were efficacious in reducing IOP among patients with uncontrolled glaucoma and ocular hypertension. Patients preferred bimatoprost over travoprost when trialed in fellow eyes.

Management of hypotrichosis of the eyelashes: Focus on bimatoprost.

Prominent eyelashes are generally recognized as enhancing beauty and are often desired by women. Until recently, the options available to augment the prominence of eyelashes were limited to makeup, over-the-counter products, artificial eyelashes, and eyelash transplantation. Originally approved for the treatment of ocular hypertension, the prostamide, bimatoprost, is now approved for the treatment of hypotrichosis of the eyelashes. Bimatoprost ophthalmic solution 0.03%, applied once daily to the skin of the upper eyelid margin using sterile single-use-per-eye applicators, increases eyelash growth, including length, thickness, and darkness. The effectiveness of bimatoprost for eyelash growth has been demonstrated by clinician ratings, digital image analysis, and patient-reported measures of satisfaction. The effects of bimatoprost treatment on eyelash length, thickness, and darkness are believed to result from longer anagen duration, increased hair bulb thickness, and increased melanogenesis, respectively. Dermally applied bimatoprost appears to be associated with a lower incidence of adverse events than administration of the medication as an eyedrop. This more favorable safety and tolerability profile is likely mediated by decreased exposure of ocular tissues to bimatoprost when applied dermally. Taken together, available data suggest that cutaneous application of bimatoprost ophthalmic solution 0.03% safely and effectively enhances upper eyelash growth.