Recent progress in prostaglandin F2α ethanolamide (prostamide F2α) research and therapeutics.

Prostamide (prostaglandin ethanolamide) research emerged from two distinct lines of research: 1) the unique pharmacology of the antiglaucoma drug bimatoprost and 2) the discovery that endocannabinoid anandamide was converted by COX-2 to a series of electrochemically neutral prostaglandin (PG) ethanolamides. Bimatoprost pharmacology was found to be virtually identical to that of prostamide F2α. The earliest studies relied on comparison of agonist potencies compared with PGF2α and synthetic prostaglandin F2α (FP) receptor agonists. The subsequent discovery of selective and potent prostamide receptor antagonists (AGN 211334-6, as shown in Fig. 3) was critical for distinguishing between prostamide and FP receptor-mediated effects. The prostamide F2α receptor was then modeled by cotransfecting the wild-type FP receptor with an mRNA splicing variant (altFP4).Bimatoprost is now used therapeutically for treating both glaucoma and eyelash hypotrichosis. Bimatoprost also stimulates hair growth in isolated human scalp hair follicles. A strong effect is also seen in mouse pelage hair, where bimatoprost essentially halves the onset of hair regrowth and the time to achieve full hair regrowth in shaved mice. Beyond glaucoma and hair growth, bimatoprost has potential for reducing fat deposition. Studies to date suggest that preadipocytes are the cellular target for bimatoprost. The discovery of the enzyme prostamide/PGF synthase was invaluable in elucidating the anatomic distribution of prostamide F2α. High expression in the central nervous system provided the impetus for later studies that described prostamide F2α as a nociceptive mediator in the spinal cord. At the translational level, bimatoprost has already provided therapeutics in two distinct areas and the use of both prostamide agonists and antagonists may provide other useful medicaments.

Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes.

Prostaglandin F2α analogs, commonly prescribed for glaucoma treatment, have been shown to induce side effects such as cutaneous hypertrichosis and hyperpigmentation. Therefore, these medications have theoretic applications in the treatment of alopecia and disorders of hypopigmentation. We reviewed the literature to find original studies assessing the use of prostaglandin F2α analogs in these settings. Studies and reports were analyzed in regards to androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring. Based on the results of these studies, and consideration of pathophysiologic mechanism, the most promising applications for prostaglandin F2α analogs include androgenic alopecia, chemotherapy-induced alopecia, and alopecia areata concurrently treated with corticosteroids.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial.

BACKGROUND: To compare the effect of bimatoprost and the fixed combination latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood pressure and on 24-hour ocular perfusion pressure (OPP). METHODS: 200 patients with glaucoma or ocular hypertension, controlled on the unfixed combination of latanoprost and timolol or eligible for dual therapy being not being fully controlled on monotherapy were enrolled in a randomized, double-masked, placebo-controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m., 8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of diastolic OPP (DPP)≤50, ≤40, ≤30 mmHg in the 2 groups were calculated and compared using Fisher's test. RESULTS: Mean baseline SBP and DBP were 136.5±18.3 vs 134.2±20.1 mmHg (p=0.1) and 79.1±10.2 vs 78.2±10.1 mmHg (p=0.4) in the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher for bimatoprost (135.1 mmHg vs 128.1 mmHg, p=0.04), while no statistically significant difference in DBP was found. DPP was similar in the 2 groups, and proportions of patients with at least one value of the 24-hour curve≤50, ≤40, ≤30 mmHg were 94%, 86%, 41% respectively. CONCLUSIONS: Bimatoprost and LTFC had similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the percentage of "dippers" was considerably higher than the one described in previous studies on the role of perfusion pressure in glaucoma. TRIAL REGISTRATION: NCT02154217, May 21, 2014.

Influence of local application of glaucoma medications-travoprost eye drops on patients' tear film function.

This study discussed about the influence of local application of glaucoma medications -- travoprost eye drops to patients' tear film function. We selected 24 patients, 45 eyes with primary open-angle glaucoma or intraocular hypertension. All of the patients topically used the travoprost eye drops for one time every night. After and before the pharmacy, we proceeded 1, 2, 3 mo lines symptom score and Schirmer's test (St), corneal fluorescein staining (FL), breakup time of tear film (BUT). Average value of symptom score and FL of all the patients before pharmacy were 1.32 ± 1. 55, 0.42 ± 0.68, and 1, 2, 3mo after pharmacy were respectively 2.68 ± 1.59, 0.96 ± 0.81; 4.97 ± 1.62, 1.46 ± 0.62; 6.21 ± 1.33, 1.88 ± 0.44. Symptom score and FL of 1, 2, 3 mo patients after pharmacy were all prominent higher than it before pharmacy (P=0.00), and it gradually increased. The average value of patients symptom BUT and St before pharmacy were (7.71 ± 0.87s), (8.32 ± 2.63mm /5min) and 1, 2, 3 mo after pharmacy were respectively (6.93 ± 1.17s), (7.69 ± 3. 33mm /5min); (5.48 ± 1.29s), (6.79 ± 2.94mm /5min); (4.33 ± 1.83s), (5.98 ± 3.11mm/5min). BUT and St value after pharmacy were prominent all lower than the level before pharmacy (P=0.00). And it gradually reduced. Short-term use of travoprost eye drops would aggravate the corneal irritation of patients, and decrease the tear film stability and tear secretion.

The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias.

Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F(2α)-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F(2α) analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.

Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension.

OBJECTIVE: To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension. DATA SOURCES: A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications. STUDY SELECTION AND DATA EXTRACTION: In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected. DATA SYNTHESIS: A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively. CONCLUSIONS: Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

Long-term utility and durability of the therapeutic effects of bimatoprost 0.03% for eyelash augmentation in healthy Asian subjects.

BACKGROUND: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. OBJECTIVE: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. METHODS: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physician's Global Eyelash Assessment and patient satisfaction. RESULTS: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. CONCLUSION: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.

Intraocular pressure-lowering efficacy and safety of bimatoprost 0.03% therapy for primary open-angle glaucoma and ocular hypertension patients in China.

BACKGROUND: To report the clinical outcomes in Chinese patients with primary open-angle glaucoma and ocular hypertension treated with bimatoprost 0.03% therapy. METHODS: Two hundred sixty-three Chinese patients with primary open-angle glaucoma and ocular hypertension who needed initial or additional intraocular pressure (IOP) lowering were recruited in this prospective, open-label, multicenter clinical study and were treated with bimatoprost 0.03%. Patients received bimatoprost 0.03% as initial, replacement or adjunctive IOP-lowering therapy, and follow-up visits were performed at week 1, and month 1 and 3 of the bimatoprost treatment. The efficacy outcome measure was the post-treatment IOP level. The safety outcome measures included the rate of medication-related symptoms, physical signs, reported adverse events, and the level of conjunctival hyperemia. RESULTS: Among 240 patients who could be categorized by pre-existing therapies and the bimatoprost therapy regimen in the study, IOP values observed in all medication conditions showed significant IOP reduction at all study visits compared with baseline. At 3 months, 8.0 ± 3.7 mmHg (32.0%) reduction in IOP was observed in treatment-naive patients after bimatoprost monotherapy; in the patients previously on various therapy regimens, 1.9 ± 2.8 mmHg (9.5%) to 6.4 ± 6.1 mmHg (24.8%) additional IOP lowering was achieved after switching to bimatoprost monotherapy or bimatoprost combination therapy. The most common adverse event was conjunctival hyperemia, mainly of trace and mild intensity. CONCLUSIONS: Our results show that bimatoprost 0.03% was effective in lowering IOP with favorable safety in Chinese primary open-angle glaucoma and ocular hypertension patients.

Bimatoprost 0.01% in treatment-naïve patients with open-angle glaucoma or ocular hypertension: an observational study in the Korean clinical setting.

BACKGROUND: This study evaluates the efficacy and tolerability (ie, occurrence and severity of hyperemia) of bimatoprost 0.01% in treatment-naïve patients with open-angle glaucoma (OAG) or ocular hypertension in the Korean clinical setting. METHODS: In this multicenter, open-label, observational study, treatment-naïve patients with OAG, including patients with normal-tension glaucoma (NTG, defined as IOP ≤21 mm Hg), or ocular hypertension received bimatoprost 0.01% once daily. Hyperemia was assessed at baseline and weeks 6 and 12, graded by a masked evaluator using a photonumeric scale (0, +0.5, +1, +2, +3), and grouped as (0 to +1) and (+2 to +3). Shifts between groupings were reported as no change, improved ([+2 to +3] to [0 to +1]), or worsened ([0 to +1] to [+2 to +3]). Other adverse events were monitored. Mean IOP changes from baseline at weeks 6 and 12 were reported. Supplemental analyses were conducted for IOPs >21 versus ≤21 mm Hg. RESULTS: Of 295 treatment-naïve patients included in the intent-to-treat/safety population, 73 (24.7%) had baseline IOP >21 mm Hg (mean, 25.7 ± 5.0 mm Hg) and 222 (75.3%) had baseline IOP ≤21 mm Hg (mean, 16.3 ± 3.0 mm Hg); 96.3% had hyperemia graded none (36.3%) to mild (17.3%). At week 12, hyperemia was graded none to mild in 83.7% (n = 220). Worsening occurred in 12.3% of patients by week 6 and 12.7% by week 12. Small improvements occurred in 0.8% and 0.5% of patients at weeks 6 and 12, respectively. Hyperemia scores were generally low and the majority of patients had no change in severity during the study. Mean IOP at weeks 6 and 12 was reduced to 16.4 ± 4.0 mm Hg (-34.5%; P < 0.0001) and 16.7 ± 3.9 mm Hg (-32.0%; P < 0.001) in the baseline-IOP >21 mm Hg group versus 13.3 ± 2.6 mm Hg (-17.8%; P < 0.001) and 13.7 ± 2.8 mm Hg (-15.9%; P < 0.001) in the baseline-IOP ≤21 mm Hg group, respectively. CONCLUSIONS: In treatment-naïve patients, bimatoprost 0.01% induced low shifts in worsening of hyperemia and significant reductions in IOP, regardless of baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER: NCT01594970.

Late-day intraocular pressure-lowering efficacy and tolerability of travoprost 0.004% versus bimatoprost 0.01% in patients with open-angle glaucoma or ocular hypertension: a randomized trial.

BACKGROUND: Medications to control intraocular pressure (IOP) are frequently preserved using benzalkonium chloride (BAK), which can negatively affect the ocular surface. Data are needed to assess efficacy and safety of prostaglandin drugs preserved with and without BAK. The present study compared the efficacy and safety of BAK-free travoprost 0.004% (TRAV) and BAK 0.02%-preserved bimatoprost 0.01% (BIM) during late-day time points in patients with open-angle glaucoma or ocular hypertension. METHODS: This was a 12-week, phase 4, randomized, investigator-masked, crossover study. 84 patients with IOP ≥24 and <36 mmHg were randomized 1:1 to receive once-daily TRAV or BIM for 6 weeks followed by an additional 6-week crossover period. IOP was measured at the end of each treatment period at 4, 6, and 8 pm. TRAV was considered noninferior to BIM if the upper limit of the 95% CI of the between-group difference in mean IOP was ≤1.5 mmHg. Adverse events were assessed throughout the study. RESULTS: One patient discontinued due to allergic conjunctivitis, and 2 patients with missing data were excluded; 81 patients were included in the per-protocol population (mean ± SD age, 58.3 ± 11.4 years; TRAV/BIM, n = 41; BIM/TRAV, n = 40). After 6 weeks, mean IOP with TRAV (17.4 ± 2.7 mmHg; change from baseline, -6.0 mmHg) was similar to BIM (17.2 ± 2.6 mmHg; change from baseline, -6.3 mmHg); the between-group difference was 0.22 mmHg (95% CI, -0.22 to 0.67). Thus, noninferiority of TRAV versus BIM was demonstrated. Mean IOP at each time point and mean and percentage IOP change from baseline were not significantly different between treatments. All treatment-emergent adverse events were mild to moderate. The incidences of mild ocular hyperemia with TRAV and BIM were 31% and 39%, respectively; moderate hyperemia was observed in 2% of patients receiving BIM. CONCLUSION: Late-day IOP-lowering efficacy of BAK-free TRAV was noninferior to that of BAK 0.02%-preserved BIM; both reduced baseline IOP by 25%. Both treatments were well tolerated, although a higher incidence of moderate ocular hyperemia was observed with BIM. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01464424; registered November 1, 2011.

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study).

BACKGROUND: Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. METHODS: A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. RESULTS: Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (

Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study.

BACKGROUND: Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. METHODS: In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. RESULTS: Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups. CONCLUSIONS: In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).

A retrospective review and observational study of outcomes and safety of bimatoprost ophthalmic solution 0.03% for treating eyelash hypotrichosis.

BACKGROUND: The efficacy and safety of bimatoprost ophthalmic solution 0.03% for treating hypotrichosis were shown in a randomized controlled trial and in an open-label study. To date, no data on real-world experience have been published. OBJECTIVE: To evaluate long-term patient satisfaction, usage patterns, and safety of bimatoprost 0.03% in clinical practice. MATERIALS AND METHODS: In this retrospective chart review with a cross-sectional design, adult patients exposed to bimatoprost 0.03% for at least 12 months were randomly sampled from 16 investigational sites. Charts were reviewed for medication usage characteristics and adverse events (AEs). At a study visit, questionnaires eliciting patient-reported outcomes were administered and spontaneously reported AEs were tabulated. RESULTS: Analysis included 585 subjects with a mean (SD) treatment duration of 19.3 (4.3) months. Patient satisfaction with bimatoprost 0.03% was 92.5%; on average, approximately 3 applications per week maintained benefits. Overall, 27.4% of patients spontaneously recalled experiencing AEs while on treatment; however, patient charts showed that only 4 AEs were documented. No instances of iris hyperpigmentation occurred. No serious or severe AEs were noted. CONCLUSION: Treatment with bimatoprost 0.03% for at least 12 months is safe, and long-term use is associated with a high degree of satisfaction.

Accidental overdose of travoprost.

PURPOSE: To report systemic symptoms after an overdose of travoprost. CASE REPORT: We report a patient who, instead of artificial tears, inadvertently used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis) surgery. She experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding, which subsided quickly upon discontinuation of the drug. CONCLUSIONS: Because of the few systemic adverse effects, prostaglandin analogs are widely used for the treatment of glaucoma. Travoprost should be taken once daily; therefore, overdose is extremely uncommon. Systemic prostaglandins have been found to be mediators of uterine activity and are used to induce labor and terminate pregnancies. The high dose of this topical medication, as well as the compromised cornea, makes this case unique. The unusual circumstances observed in this case greatly expand our knowledge regarding the potential adverse effects of travoprost.

Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost.

BACKGROUND: To investigate the frequency of prostaglandin-associated periorbitopathy among bimatoprost, latanoprost and travoprost users. DESIGN: Retrospective observational case series. PARTICIPANTS: The study group included 105 patients who were using one of the drugs in one eye for more than 1 month, and the other eye was used as a control. MAIN OUTCOME MEASURES: The frequency of prostaglandin-associated periorbitopathy. METHODS: Special care was taken to detect five prostaglandin-associated periorbitopathy findings. Hertel exophthalmometry measurements and colour pictures of the periocular area were taken. RESULTS: Statistically significant differences were found among the groups regarding the presence of all prostaglandin-associated periorbitopathy findings (P < 0.05). Periorbital fat loss was the most frequent and was observed in nearly all prostaglandin-associated periorbitopathy patients except those who were relatively young. The overall frequency of prostaglandin-associated periorbito pathy was 93.3% in the bimatoprost group, 41.4% in the latanoprost group and 70% in the travoprost group. The frequency of deepening of the upper lid sulcus was 80% in the bimatoprost group, 15.7% in the latanoprost group and 45% in the travoprost group. The frequency of milder changes (the presence of either only periorbital fat loss or dermatochalasis involution or the presence of both) was higher in the latanoprost group (62%) than in the travoprost (35.7%) and bimatoprost (7.1%) groups. CONCLUSIONS: Prostaglandin-associated periorbitopathy is as common as other adverse effects when careful examinations are performed and is more frequent and more severe in bimatoprost users. The loss of the periorbital fat pad is the first sign to occur during the evolution of prostaglandin-associated periorbitopathy, especially in older patients.

Skin graft hypertrichosis associated with prostaglandin analog in the treatment of glaucoma.

Prostaglandin analogs are commonly used in the treatment of glaucoma. They are a safe and effective treatment associated with few side effects. Common local side effects include conjunctival hyperemia, iris pigmentation, and eyelash hypertrichosis. The authors present a case of a patient using travoprost treatment for primary open-angle glaucoma, who underwent excision of a lower eyelid basal cell carcinoma and reconstruction with an upper eyelid tarsoconjunctival flap and overlying skin graft. The patient developed hypertrichosis of the skin graft attributable to prostaglandin analog use.

Bimatoprost for eyelash growth in Japanese subjects: two multicenter controlled studies.

BACKGROUND: Bimatoprost 0.03% has enhanced eyelash prominence in clinical trials enrolling mostly Caucasian subjects. The studies described in this report evaluated the efficacy and safety of bimatoprost in Japanese subjects with idiopathic and chemotherapy-induced eyelash hypotrichosis. METHODS: In two multicenter, double-masked, randomized, parallel-group studies (study 1: n=173 [idiopathic]; study 2: n=36 [chemotherapy-induced]), subjects received bimatoprost 0.03% or vehicle applied once daily to the upper eyelid margins. The primary efficacy measure was eyelash prominence measured by Global Eyelash Assessment (GEA) scores. Additional measures were eyelash length, thickness, and darkness, assessed by digital image analysis, and patient satisfaction (Eyelash Satisfaction Questionnaire-9). Safety assessments included adverse-event monitoring and ophthalmic examinations. RESULTS: Significantly more bimatoprost-treated subjects had at least a one-grade improvement in GEA score from baseline to month 4 compared with vehicle in study 1 (77.3 vs 17.6%; P<0.001) and study 2 (88.9 vs 27.8%; P<0.001). Bimatoprost-treated subjects had significantly greater increases in eyelash length, thickness, and darkness at the primary time point (month 4 in both studies; all P<0.001, study 1; P≤0.04, study 2). The bimatoprost group showed greater subject satisfaction in both studies. The incidence of adverse events was similar in the two groups. Ophthalmic examination showed slightly greater mean reductions in intraocular pressure (IOP) with bimatoprost than with vehicle, and the reductions were within the normal range for daily IOP fluctuations. CONCLUSION: Bimatoprost 0.03% was shown to be effective and safe in these studies of Japanese subjects with eyelash hypotrichosis. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Application of bimatoprost ophthalmic solution 0.03% for the treatment of eyebrow hypotrichosis: series of ten cases.

In December 2008, bimatoprost ophthalmic solution 0.03% was approved in the United States for the treatment of hypotrichosis of the eyelashes. Since then, there have been several reports in the literature on the off-label use of bimatoprost ophthalmic solution 0.03% for the treatment of thinning in other hair bearing areas, such as in the eyebrows and in the scalp. Herein, a prospective pilot study is presented in which bimatoprost ophthalmic solution 0.03% is evaluated for helping to re-grow hair in the eyebrow region of ten female patients.

[Evaluation of the effectiveness of Ganfort treatment in patients with secondary neovascular glaucoma associated with diabetes mellitus].

PURPOSE: To evaluate the effectiveness of bimatoprost/timolol fixed combination (Ganfort) in decreasing intraocular pressure (IOP) in patients with diabetes mellitus (DM) and uncontrolled secondary neovascular glaucoma (NG). MATERIAL AND METHODS: The study included 50 patients (51 eyes) with diabetes mellitus and sings of uncontrolled secondary NG, which was later confirmed by the results of ophthalmological assessment. All the patients were offered to change their IOP-lowering medications and if the new regimen is still ineffective--to undergo drainage surgery. Therefore they were switched to Ganfort once daily in the morning. RESULTS: After switching the therapy a decrease of intraocular pressure was observed in 100% of cases. In 72.5% of patients (37 eyes) the average IOP was almost 3 times lower than at the baseline and achieved target values (15-17 mm Hg), thus allowing to avoid surgical intervention. In 27.5% of patients (14 eyes), despite a significant decrease of IOP, surgical treatment was considered still necessary due to glaucoma progression and, therefore, drainage surgery was performed. CONCLUSION: The IOP-lowering combination Ganfort (Allergan) can be used in patients with secondary neovascular glaucoma and diabetes mellitus as the treatment of choice. Even if target IOP is not achieved, Ganfort is still useful as a preoperative medication able to reduce postoperative hemorrhagic complications.

A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study.

PURPOSE: To compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. METHODS: 691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. RESULTS: 661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia. CONCLUSION: The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.