Search

Purpose: To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system. Methods: Patients with OAG/OH and OSD were randomized to treatment with PF-latanoprost-E or travoprost-Z nightly for 3 months. Outcomes included mean diurnal IOP reduction; OSD endpoints, including symptom improvement, tear break-up time (TBUT), and corneal fluorescein staining (CFS) score; and safety after 1 and 3 months. Results: A total of 105 patients were randomized, 51 to PF-latanoprost-E and 54 to travoprost-Z. IOP reductions (LS mean differences) at 3 months were numerically greater in the PF-latanoprost-E than in the travoprost-Z group at 8AM (7.2 versus 6.0 mmHg), 10AM (6.7 versus 5.9 mmHg), and 4PM (6.0 versus 5.4 mmHg). LS mean changes in IOP from baseline in both groups at 1 and 3 months, however, were comparable. Mean ± SD CFS scores on the Ora scale at month 3 showed significantly greater reductions in the PF-latanoprost-E than in the travoprost-Z group (-1.07 ± 1.863 versus -0.16 ± 2.553 P = 0.0461). The mean TBUT at month 3 showed similar improvements in both groups (1.1 versus 1.0 s, P > 0.05). OSD symptoms improved but did not differ significantly in the two groups. Overall safety was comparable in both groups. Conclusion: PF-latanoprost-E effectively and safely lowered IOP and improved OSD parameters in patients with OAG/OH. These findings provide evidence for the beneficial effects of this new formulation of latanoprost in glaucoma patients with OSD.

English Summary: Glaucoma is a leading cause of the global prevalence of irreversible blindness. The pathogenesis of glaucoma is not entirely known, but the major risk factors include advancing age, genetic predisposition, and increased intraocular pressure (IOP). The only evidence-based treatment is a lowering of IOP through the use of eye drops, laser procedures, or surgical interventions. Although laser treatment is gaining recognition as a first-choice treatment option, the most common approach for managing glaucoma is IOP-lowering eye drops. A major challenge in the treatment is the occurrence of adverse events and poor adherence. In this context, the ocular surface is an area of great concern, as most glaucoma patients have dry eye disease (DED), which is largely caused by eye drops. Preservation with benzalkonium chloride (BAK) is a controversial topic due to its potential role as a significant cause of DED. A systematic review and meta-analyses investigate potential differences in efficacy and safety between BAK-preserved and BAK-free anti-glaucomatous eye drops (I). Many of the included studies report on ocular surface damage caused by the application of BAK-preserved eye drops. However, the meta-analyses addressing hyperemia, number of ocular adverse events, and tear break-up time did not identify any significant differences. The latter is likely due to varying measurement methods, different endpoints, and study durations. It is, therefore, possible that the large variations between the studies conceal differences in the safety profiles. The efficacy meta-analysis finds that there are no differences in the IOP-lowering effect between BAK-preserved and BAK-free eye drops, indicating that BAK is not necessary for the effectiveness of eye drops. To promote more homogeneous choices of endpoints and methods when evaluating BAK-preserved and BAK-free glaucoma treatments, a Delphi consensus statement was performed. In this study, glaucoma experts and ocular surface disease experts reached consensus on the key factors to consider when designing such studies (II). The hope is to have more studies with comparable endpoints that can systematically show the potentially adverse effects of BAK. The preclinical studies in the current Ph.D. research focus on conjunctival goblet cells (GCs). GCs are important for the ocular surface because they release the mucin MUC5AC, which is an essential component of the inner layer of the tear film. BAK preservation may damage the GCs and result in a low GC density, leading to an unstable tear film and DED. The most commonly used IOP-lowering drugs are prostaglandin analogs (PGAs). Thus, the conducted studies investigate the effect of PGAs preserved in different ways on GCs. BAK-preserved latanoprost is cytotoxic to primary cultured human conjunctival GCs and results in a scattered expression of MUC5AC, in contrast to negative controls, where MUC5AC is localized around the cell nucleus (III). Preservative-free (PF) latanoprost is not cytotoxic and does not affect the MUC5AC expression pattern. Furthermore, BAK-preserved travoprost is found to be cytotoxic in a time-dependent manner, while Polyquad®-preserved travoprost does not affect GC survival at any measured time point (IV). Both Polyquad and BAK induce scattered expression of MUC5AC. The cytotoxicity of BAK-preserved PGA eye drops is higher compared to the safer profile of PF and Polyquad-preserved PGA eye drops (V). Additionally, PF latanoprost does not increase the release of the inflammatory markers interleukin (IL)-6 and IL-8, unlike BAK-preserved latanoprost. A review highlights the active and inactive components of IOP-lowering eye drops (VI). Several preclinical and clinical studies have identified adverse effects of BAK. Although other components, such as the active drug and phosphates, can also cause adverse events, the review clearly states that BAK alone is a major source of decreased tolerability. The conclusion of this thesis is that BAK preservation is unnecessary and harmful to the ocular surface. The preclinical studies demonstrate that GCs die when exposed to BAK. Furthermore, they find that BAK induces a pro-inflammatory response. The review included in the thesis concludes that BAK should be phased out of eye drops for chronic use. Overall, the inclusion of BAK poses a risk of developing DED and poor adherence, which can ultimately lead to disease progression and blindness., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Here is presented a unique case of bilateral serous macular detachments as a side effect of topical travoprost (0.004%) therapy. Only three other cases in the literature have definitively associated this side effect with other topical prostaglandins. The aetiological and pathophysiological pathways remain to be clearly elucidated but are potentially related to increased choroidal vascular permeability. In this case, the subretinal fluid resolved rapidly and completely after cessation of travoprost drops, showing it to be a reversible pathology similar to prostaglandin-associated cystoid macular oedema. This uncommon association is therefore important to consider in the differential diagnosis of serous macular detachment. Increasing ophthalmic awareness could help to prevent unnecessary investigations in undifferentiated patients without other guiding historical or examination features. This may save time and expense for the patient and health systems., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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 ± standard deviation, 69.9 ± 14.5 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 ± 5.4 mm Hg) than grades 0 (15.0 ± 5.1 mm Hg, P = .032) and 1 (14.5 ± 4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ± 3.2 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 ± 0.8) and bimatoprost (2.0 ± 0.7) than latanoprost (1.0 ± 0.8, P < .001 for both comparisons) and tafluprost (1.0 ± 0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ± 0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard β = 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., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Purpose: Preservatives in glaucoma medications have been associated with ocular toxicity. We compared ocular signs and symptoms in patients with open-angle glaucoma or ocular hypertension treated in monotherapy with preserved or preservative-free prostaglandin analogues., Methods: Observational cross-sectional clinical study in real life. 82 patients treated for at least 6 months with prostaglandin analogue were assessed for intraocular pressure, ocular symptoms and ocular signs including conjunctival hyperaemia, tear break-up time and tear meniscus height measured using objective and non-invasive methods (OCULUS Keratograph 5M). Patients presenting with symptoms of ocular toxicity with preserved prostaglandin analogues were switched to preservative-free latanoprost, and a second assessment was processed 6 months after., Results: At inclusion, 30 (36.6%) patients were treated with preservative-free latanoprost, 25 (30.5%) with preserved latanoprost, 16 (19.5%) with preserved travoprost and 11 (13.4%) with preserved bimatoprost. Patients treated with preservative-free latanoprost reported significantly less ocular symptoms upon instillation (mainly burning) and between instillations than patients treated with preserved prostaglandin analogues. The mean conjunctival hyperaemia (limbal + bulbar) was significantly lower with preservative-free latanoprost (2.08 ± 0.55) compared to preserved latanoprost (2.50 ± 0.7, p = 0.0085), preserved travoprost (2.67 ± 0.82, p = 0.0083) and preserved bimatoprost (2.68 ± 0.67, p = 0.0041). There were no relevant between-group differences in mean tear meniscus height and break-up time. Ocular symptoms and conjunctival hyperaemia improved when preserved prostaglandin analogues were switched to preservative-free latanoprost for 6 months while intraocular pressure reduction was maintained., Conclusion: Overall, this study suggests a better subjective and objective ocular tolerance when patients were treated with preservative-free latanoprost than with other preserved prostaglandin analogues monotherapy. Switching to preservative-free latanoprost maintained intraocular pressure at the same level as preservative prostaglandin analogue, but improved ocular surface tolerance.

Purpose: To evaluate the efficacy and safety of travoprost 0.004% versus timolol 0.5% as an initial intraocular pressure (IOP)-lowering medication for ocular hypertension secondary to vitrectomy., Patients and Methods: We performed a randomized, controlled, observer-blinded clinical trial in the Eye & ENT Hospital of Fudan University in China. This trial was registered at www.chictr.org.cn (ChICTR1800014942) before patient enrollment. Seventy-nine adults with IOP of 25-45 mmHg secondary to vitrectomy in the latest one month were enrolled and randomized to receive travoprost 0.004% or timolol 0.5%. More drugs were administered to patients with IOP > 25 mmHg during follow-up., Results: The mean IOP reduction at day 1 was -10.97 mmHg in the timolol group and -15.02 mmHg in the travoprost group ( P = 0.006); no significant difference was observed between the groups at later time points. The number of IOP-lowering medications at day 21 was 0.64 in the timolol group and 1.15 in the travoprost group ( P = 0.038), while no significant differences were observed at other time points. The proportion of single IOP-lowering medications used during the 4-week follow-up was 72.73% in the timolol group and 68.42% in the travoprost group ( P = 0.692). Inflammation scores were not significantly different in the two groups at any time point. Increased ocular hyperemia occurred in 8 patients (19%) in the travoprost group and none in the timolol group ( P = 0.005). There were no significant differences in other adverse events between the two groups. After logistic regression model analysis, IOP ≥ 30 mmHg, inflammation score ≥ 2, and silicone oil as tamponade were found to be the factors with significant effects on the number of IOP-lowering medications used during the 4-week follow-up., Conclusion: Travoprost and timolol have similar efficacy and safety for treating ocular hypertension secondary to vitrectomy., Competing Interests: The authors report no conflicts of interest with this work., (© 2019 Fang et al.)

Background: This study will evaluate the efficacy of travoprost for patients with glaucoma systematically., Methods: A comprehensive literature search will be carried from following literature sources from inception to the present: Cochrane Library, MEDLINE, EMBASE, Web of Science, Google scholar, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will only consider randomized controlled trials on assessing the efficacy and safety of travoprost for glaucoma for inclusion. We will use Cochrane risk of bias tool for the methodological quality assessment for each qualified study. If it is possible, we will pool the outcome data, and will perform meta-analysis., Results: This study will systematically evaluate the efficacy and safety of travoprost for glaucoma. Primary outcomes include intraocular pressure (IOP), mean IOP, and mean reduction of IOP. Secondary outcomes consist of diastolic ocular perfusion pressure, central corneal thickness, and quality of life, as measured by 36-Item Short Form Health Survey, and treatment-related adverse events included hyperemia, eye pain, and eye pruritus., Conclusion: The findings of the present study will summarize the updated evidence of travoprost for patients with glaucoma.PROSPERO registration number: PROSPERO CRD42019126956.

Background: Eyelashes have both a protective and an aesthetic function. Hypotrichosis of the eyelashes may negatively influence an individual's self-perception., Objective: To evaluate efficacy and safety of topical administration of a new cosmetic preparation containing 15 keto fluprostenol isopropyl ester (80 µgr/mL) for the treatment of idiopathic hypotrichosis of the eyelashes., Methods: This is a monocentric, double-blind, vehicle-controlled study. Forty patients (18 years) with idiopathic hypotrichosis (GEA 1 or 2), who also exhibit feelings of low confidence, based on the ESQ score, were divided into two groups. Group 1: twenty women treated with once-daily 15 keto fluprostenol isopropyl ester gel and Group 2: twenty women treated only with the vehicle gel., Results: Group 1: The average difference in eyelash length measured at the midpoint of palpebral margins between T0 and T2 for Group 1 was 1633 mm and for Group B was 0.25 (P < 0.0001). Comparing the ESQ questionnaires of Groups 1 and 2 from T0 to T2, only the 80% of the patients of Group 1 declared to dedicate less time to the application of cosmetic mascara, having longer and darker lashes at T2 vs patients of Group 2, of which only 20% reported longer and darker eyelashes at T2. About safety, only one patient of Group 1 experienced sensation of ocular sensation heaviness and headache. No other side effects were referred., Conclusions: 15 keto fluprostenol isopropyl ester gel was effective in enhancing eyelash growth, with an excellent safety profile., (© 2019 Wiley Periodicals, Inc.)

Purpose: To study the hypotensive efficacy and safety of Travapress (0.004% travoprost) in patients with primary open-angle glaucoma (POAG)., Material and Methods: The study included 50 patients (91 eyes) aged 45 to 74 years. The first group consisted of 23 patients (41 eyes) who received monotherapy with Travaprost. Patients of the second group (27 patients, 50 eyes) Travaprost was added to therapy with timolol 0.5% (17 patients, 32 eyes) or dorzolamide 2% (10 patients, 18 eyes). Travaprost was given for a period of 6 months. IOP was determined in 2 weeks, 1, 3 and 6 months from the beginning of treatment and daily IOP measurement was at 10.00, 12.00, 14.00 and 16.00. Subjective symptoms were evaluated in points by special scales., Results: The study was completed by 42 patients (84%, 79 eyes). Two patients (4.7%) has stopped to use Travapress due to the side effects. Local side effects were observed in 9 patients (21.4%) with mild hyperemia being the most common and seen in 5 patients (11.9%). In the first group, the maximum IOP decrease was recorded for 3 months of the study and amounted to 7.3±1.2 mm Hg (27.5%) compared to baseline. By 6 months, IOP decreased by 6.8±1.5 mm Hg on average (25.6%). In the second group in the subgroup with timolol 0,5% IOP decreased by 4,9±1.7 mm Hg (20%) compared to baseline, in the subgroup with dorzolamid 2% - by 4,3±1,3 mm Hg (16,9%) compared to baseline. Evening use the drug was accompanied by significantly lower levels of daily IOP fluctuations compared with morning intake (3.0±1.2 and 3.8±1.7 mm Hg, respectively, p = 0,002)., Conclusion: Travapress was established as highly efficient and safe. It can be recommended for wide use in the treatment of patients with POAG.

Purpose: To assess ocular surface changes in participants using latanoprost with benzalkonium chloride (Xalatan) and travoprost with SofZia (Travatan Z)., Methods: In this prospective, open-label, nonrandomized cohort study, participants were classified into two groups: group 1 (n=28) naive to glaucoma therapy, group 2 (n=27) on previous Xalatan monotherapy in both eyes. Both groups started (or continued) Xalatan in the right eye and Travatan Z in the left eye. Baseline, 1-, and 2-month measurements of tear breakup time (TBUT), corneal staining score, conjunctival staining score, conjunctival hyperemia score, tear production, and intraocular pressure were obtained. The Ocular Surface Disease Index questionnaire measured participants' comfort and dryness symptoms. Medication preference was recorded., Results: Data were collected from 55 participants. Tear breakup time at baseline and 1-month follow-up in group 1 was significantly longer than that of group 2 (P=0.005). At 2 months, there was no significant difference in TBUT between the two groups (P=0.779). Tear production in group 1 at all three time points was significantly higher than group 2 (P<0.05). Conjunctival staining score at 2 months in group 1 was significantly higher than group 2 (P=0.031). There was no significant difference in other parameters between the groups at any other time point. No significant difference in any parameter was found between Xalatan and Travatan Z (intragroup comparison)., Conclusions: Significant differences in ocular surface characteristics were detected between groups, but no significant difference was detected between participants treated with Xalatan and Travatan Z.

Purpose: To report the rare incidence of retinal pigment epithelial detachment (RPED) followed by topical travoprost therapy and its subsequent reattachment after cessation of the drug., Methods: A 60-year-old male presented with gradual loss of vision in both eyes and distorted images in right eye. He gave a history of visiting an ophthalmologist a week ago for a routine eye examination. His previous reports revealed best-corrected visual acuity (BCVA) of 6/6, N6 in both eyes with raised intraocular pressures. A diagnosis of primary open-angle glaucoma was made and prescribed topical travoprost 0.004% eye drops. This patient's subsequent visit with diagnosis and treatment is mentioned in this case report., Results: On examination, his BCVA was found to be 6/36, N12 and 6/6, N6 in right and left eyes, respectively. Optical coherence tomography (OCT) macular scan revealed RPED involving fovea in the right eye and inferotemporal to fovea in the left eye. Patient was advised to discontinue topical travoprost and started brinzolamide 1% eye drops. Ten-day follow-up visit revealed partially resolved RPED by OCT with 6/9 and 6/6 visual acuity in the right and left eyes, respectively. After 1 month, reversal of RPED was noted in OCT with 6/6 vision in both eyes., Conclusion: Hence, clinicians should be aware of this rare incidence of RPED followed by travoprost therapy. First case of RPED following travoprost therapy and complete reattachment upon withdrawal is reported here in this case report.

Purpose: To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs)., Materials and Methods: In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD., Results: PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05)., Conclusions: PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

Objective: To describe the prevalent side effects of prostaglandin analogues (PA) in a Hispanic population and their effect on quality of life (QOL)., Patients and Methods: This is a cross-sectional study conducted in a tertiary medical facility in which patients were evaluated in a single visit. Total of 14 participants in the study, 10 women and 4 men. Ages ranged from 26-78 years old. Subjects underwent a single full Oculoplastic evaluation by two physicians; one was blinded on patient medical history and assessed for PA side effects. After evaluation, each study subject was asked to answer a self reported QOL questionnaire., Results: Study participants had used or were currently using Bimatoprost (28.6%), Latanoprost (50%) or Travoprost (21.4%). After evaluate periorbital changes, 2 patients (14.3%) had ptosis, 2 (14.3%) had periorbital skin hyperpigmentation, 11 (78.6%) had periorbital fat show, 11 (78.6%) had eyelash elongation, 1 (7.1%) had injected conjunctiva, 5 (35.7%) had iris hyperpigmentation. 10 (71.4%) noted changes in the size/shape of their eyes. The questionnaire show that 10 (71.4%) disliked how their eyes looked. 9 (62.4%) reported dry eyes, 3 (21.4%) noted increased need to blink, 5 (35.7%) reported foreign body sensation, 7 (50%) reported burning sensation, 2 (14.2%) reported secretions and 3 (21.4%) reported sticky eyes. Mean QOL was 3.50, 2.14, and 2.00 in the Bimatroprost, Latanoprost, and Travoprost users respectively., Conclusion: QOL questionnaire showed that Bimatoprost side effects had the most negative impact in QOL, followed by the Latanoprost and Travoprost groups.

Purpose: To evaluate efficacy and safety of travoprost in pediatric patients with ocular hypertension or glaucoma and demonstrate its noninferiority to timolol., Methods: Patients aged 2 months to <18 years with glaucoma or ocular hypertension were randomized to receive travoprost (0.004%) or timolol eye drops (0.25% for patients aged 2 months to <3 years and 0.5% for patients ≥3 years old) for 3 months in this double-masked, parallel-group study. Intraocular pressure (IOP) was measured and patients were evaluated at 2 weeks, 6 weeks, and 3 months after treatment. Change in IOP from baseline to 3 months was the primary endpoint, and the test of noninferiority was based on a margin of +3.0 mm Hg using the 95% 2-sided confidence interval of the mean change., Results: Of 157 patients included (mean age, 9.6 years), 77 received travoprost and 75 timolol. All patients experienced a significant reduction in IOP in the study eye at 3 months: the mean IOP change from baseline was -5.4 mm Hg for travoprost; -5.3 mm Hg, for timolol. The mean difference between travoprost and timolol at month 3 was -0.1 mm Hg (95% CI, -1.5 to 1.4 mm Hg). The most common treatment-related adverse events for the travoprost group were ocular hyperemia and eyelash growth. No serious adverse events were reported., Conclusions: This study found travoprost to be noninferior to timolol in lowering IOP in patients with pediatric glaucoma or ocular hypertension. Travoprost was well-tolerated, and no treatment-related systemic adverse events were reported., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004% preserved with Polyquad ® (TRAVATAN ® ) in pediatric patients with glaucoma or ocular hypertension., Methods: This was a phase 1, open-label, multicenter clinical study of patients aged ≥2 months to <18 years. Patients received daily administration of travoprost 0.004% preserved with Polyquad in both eyes for 7 days. Plasma samples were collected 30 min before the final dose and at 10, 20, 40, and 80 min postdose. The main outcome measure was maximum concentration of travoprost free acid in plasma (C max )., Results: Included in the PK analysis were 24 patients (average age 9.6 ± 4.9 years). At least 1 sample with quantifiable levels of travoprost free acid was collected for 11 patients. The mean C max was 0.0471 ± 0.0105 ng/mL for patients aged 2 months to <3 years; 0.0258 ± 0.0128 ng/mL for ages 3 to <12 years; and 0.0109 ± 0.0005 ng/mL for ages 12 to <18 years. Travoprost was undetectable in samples collected predose from pediatric patients. Treatment-related adverse events (AEs) included hyperemia, eye pain, and eye pruritus (n = 1 each). There were no discontinuations or drug-related serious AEs., Conclusions: Travoprost free acid concentration in plasma was low in pediatric patients, detectable in only 11 of 24 patients. There was no accumulation of travoprost over the course of treatment. No clear relationship was observed between age/body surface area and C max . No increased risk was identified for the use of travoprost 0.004% preserved with Polyquad in patients <18 years of age.

Purpose: To determine factors related to prostaglandin-associated periorbitopathy (PAP) and its prevalence in glaucoma or ocular hypertension (OHT) patients using prostaglandins analogs (PGAs)., Design: A cross-sectional study., Methods: A study of glaucoma or OHT patients, using topical PGAs for at least 3 months, was performed. Eyes treated with PGAs were photoraphed and independently evaluated for PAP by 2 glaucoma specialists using at least 4 out of 7 clinical appearances. The factors of interest were sex, age, body mass index (BMI), types of glaucoma, types of PGAs, duration of PGA use, and concurrent 0.5% timolol. Univariate (χ2 test) and multivariate (multiple logistic regression) analyses assessing risk factors for PAP were performed to estimate the odds ratios (OR) with 95% conidence intervals (CIs)., Results: One hundred thirty-four eyes from 134 patients were included. Seventy (52.2%), 21 (15.7%), and 43 (32%) eyes received components of latanoprost, travoprost, and bimatoprost, respectively. Prevalence of PAP was 44.8% (95% CI, 36.3 to 53.3). Older age >60 years (OR, 3.0; 95% CI, 1.2 to 7.8), bimatoprost (OR, 4.0; 95% CI, 1.6 to 9.5), travoprost (OR, 3.3; 95% CI, 1.1 to 10.1), and timolol (OR, 2.9; 95% CI, 1.3 to 6.8) were at risk of PAP development. In addition, BMI ≥23 kg/㎡ (OR, 0.3; 95% CI, 0.1 to 0.7) was reversely associated with PAP., Conclusions: Older age, bimatoprost, or travoprost were associated with PAP, whereas high BMI was found as a protective factor. Interestingly, timolol possibly precipitated periorbital change when in use with prostaglandins., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Purpose: To compare latanoprost/timolol (LT) versus travoprost/timolol (TT) fixed combinations for ocular hypertension (OHT) associated with uveitis., Methods: Thirty-six patients (55 eyes) who were treated with LT (28 eyes) or TT (27 eyes) for OHT associated with uveitis were reviewed retrospectively. Intraocular pressure (IOP) and inflammation scores at the initiation of treatment and at the last visit during therapy were analyzed., Results: Although IOP was reduced significantly in both LT and TT groups, the reduction rate was significantly greater with TT group than with LT. The differences in the reduction of IOP between the groups remained significant when the cases were classified into inflammation-induced OHT and steroid-induced OHT. Inflammation score was not exacerbated by LT or TT treatment., Conclusions: Both LT and TT are safe and effective for the treatment of OHT associated with uveitis and greater IOP reduction may be achieved by TT than by LT treatment.

Introduction: We examined the sustainability of the intraocular pressure (IOP)-lowering efficacy of travoprost (0.004%) ophthalmic solution in subjects with normal tension glaucoma (NTG)., Methods: Travoprost ophthalmic solution was given once daily at 9 PM to subjects with newly diagnosed NTG or with NTG who had not received any ocular hypotensives within the previous 30 days. IOP was measured at three time points (9 AM, 1 PM, and 5 PM) at baseline and week 12 visits, and at one time point (9 AM) at week 4 and week 8 visits. Conjunctival hyperemia, superficial punctate keratopathy, and other adverse events were evaluated during the observation period., Results: Thirty subjects (12 males and 18 females; mean age 65.6 years) from 32 subjects enrolled were included in the efficacy analysis. The mean IOPs (±standard deviation) of 16.6 ± 1.4, 15.7 ± 1.8, and 15.7 ± 2.2 mmHg at 9 AM, 1 PM, and 5 PM, respectively, at baseline reduced significantly to the mean IOPs of 13.0 ± 1.8, 12.7 ± 1.8, and 12.8 ± 1.6 mmHg, respectively, at week 12 (P < 0.0001 for every time point). Together with the mean IOPs of 13.4 ± 1.9 mmHg at week 4 and 13.2 ± 1.9 mmHg at week 8, the pooled IOP during the observation period for up to 12 weeks showed a statistically and clinically significant reduction of IOP at 9 AM. (3.4 mmHg or 20.3% reduction from baseline, P < 0.0001). There were no adverse events leading to treatment discontinuation., Conclusion: This multi-center collaborative study suggests that IOP-lowering efficacy of travoprost ophthalmic solution persists during the day at the clinically relevant level in subjects with NTG., Funding: Alcon Japan Ltd., Trial Registration: University Hospital Medical Information Network, UMIN ID: 000011621.

Purpose: It is reported that nonsteroidal anti-inflammatory drug (NSAID) ophthalmic solution affected the therapeutic efficacy of prostaglandin (PG) analog by inhibiting endogenous PG production. However, whether NSAID ophthalmic solution interferes with its conjunctival hyperemia is unknown. We investigated the effect of NSAID ophthalmic solution on its hyperemia., Materials and Methods: This was a prospective, randomized, double-blind, placebo-controlled 1-month trial. Benzalkonium chloride-free travoprost 0.004% was used as a PG analog and administered once daily (08:00) in both eyes. Bromfenac sodium hydrate was assigned randomly to 1 eye twice daily (08:00 and 20:00) (the NSAID side), whereas flavin adenine dinucleotide sodium was applied to the fellow eye of each patient twice daily (08:00 and 20:00) (the control side). Conjunctival photographs of both eyes were taken 3 times (08:00, 14:00, 20:00) on days 1, 2, 7, and 28, and hyperemia was scored from 0 to 5 (H-score). We compared H-scores on the NSAID and control sides., Results: Twenty-eight Japanese normal subjects completed the study. The H-score on the NSAID side was significantly lower than that on the control side on day 1 at 14:00 (P=0.016, paired t test) and day 2 at 14:00 (P=0.016). But there were no differences at 20:00 on each day and after that time., Conclusions: The use of NSAID ophthalmic solution had almost no impact on PG analog-related conjunctival hyperemia. This partly suggests that the action mechanism of endogenous PG after administrating PG analog might be no correlation with conjunctival hyperemia.

A 54-year-old Indian male with a diagnosis of ocular hypertension was started on a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six years later, he developed progressively increasing bilateral limbal conjunctival hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and over the next year, the patient's conjunctival pigmentation improved significantly in both the eyes. This case report documents with slit-lamp photography the first case of conjunctival pigmentation associated with PGA use that has been shown to have reversal with discontinuation of the PGA. Because of the widespread use of PGAs, and the evolving nature of the conjunctival pigmentation, clinicians should be aware of this reversible condition when considering biopsy or removal of conjunctival melanocytic lesions.

Background: Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK)., Methods: This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan® preserved with POLYQUAD® [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of ≤18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study., Results: All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P < 0.001 for both). A greater percentage of patients achieved a target IOP of ≤18 mmHg at week 6 (93.1 %; n = 163/175) and week 12 (93.3 %; n = 166/178) compared with baseline (89.5 %; n = 171/191). There was a 10.5 % increase in the percentage of patients with "none/trace" amounts of hyperemia. Most patients preferred the study medication (81.5 %; n = 141/173) and were confident that they would adhere to their preferred medication (90.8 %; n = 157/173). No serious AEs were reported, and eye irritation (3.7 %; n = 7/191) was the most common treatment-related AE., Conclusions: Transitioning from BAK-containing latanoprost 0.005 % to BAK-free travoprost 0.004 % preserved with PQ reduced IOP in patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues., Trial Registration: ClinicalTrials.gov identifier, NCT01510145.

Purpose: To study the effects of prostaglandin analogue drops on the eyelids and adnexa in unilaterally treated subjects with the intention of qualifying, quantifying, and categorizing the characteristics of prostaglandin-associated periorbitopathy (PAP)., Methods: Patients using prostaglandin analogue drops in only 1 eye for at least 1 year were evaluated by masked examiners. Orbital and eyelid measurements were obtained for each patient, and adnexal photographs were taken. PAP was divided into 3 grades based on the presence and severity of fat atrophy and the existence and depth of superior sulcus deformity. Statistical analysis was performed comparing data between treated and untreated eyes., Results: Thirty-three patients meeting eligibility criteria were enrolled, with equal numbers of subjects using latanoprost, travoprost, and bimatoprost. Treated eyes had a statistically significant increase in lagophthalmos (0.62 mm, p < 0.001), superior sulcus deformity/PAP grade (0.72, p < 0.001), and eyelid redness (1.08, p < 0.001). Treated eyes had significantly greater marginal reflex distance 1 measurements (0.89 mm, p = 0.02), highest with bimatoprost and moderate PAP. Treated eyes had relatively greater enophthalmos than untreated eyes. Very few patients noticed or complained about eyelid changes., Conclusion: Prostaglandin analogue drops cause adnexal changes and orbital fat atrophy leading to eyelid redness, superior sulcus deformity, higher eyelid crease, and enophthalmos. In contrast to previous studies showing ptosis in PAP, relative upper eyelid retraction was seen in most of our treated eyes. Our novel PAP grading scale may help objectify and categorize this syndrome. Awareness of these signs is critical, as the eyelids and eyes may be affected even in the absence of patient recognition.

Background: Prostaglandin-timolol fixed combinations (PG-timolol FCs) are now widely used to reduce intraocular pressure in patients with glaucoma. The efficacy and tolerability of these drugs are worthy of further exploration. An updated systematic review and meta-analysis was performed to assess the clinical efficacy and tolerability of the three PG-timolol FCs., Methods: Pertinent randomized, controlled trials were identified through systematic searches of PubMed, Embase, the Cochrane central register of controlled trials and the Chinese Biomedicine Database. The main efficacy measures were the weighted mean differences (WMDs) for the reduction from baseline to end of treatment in IOP at 9 am, 12 pm and 4 pm and diurnal curve. The main tolerability measures were the odds ratios (ORs) for the incidence of conjunctival hyperemia., Results: Nine studies involving 991 patients were included in the meta-analysis. Latanoprost-timolol FC (LTFC) and travoprost-timolol FC (TTFC) were not significantly different in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm. Bimatoprost-timolol FC (BTFC) provided significantly greater efficacy in lowering IOP at the three measurement time points and over the mean diurnal curve than LTFC (diurnal curve: WMD = 0.88 mmHg [95% CI, 0.42 to 1.33]; 9 am: WMD = 1.27 mmHg [0.68 to 1.86]; 12 pm: WMD = 1.16 mmHg [0.85 to 1.46]; 4 pm: WMD = 0.61 mmHg [0.51 to 0.70]) and TTFC (diurnal curve: WMD = 1.94 mmHg [0.19 to 3.68]; 9 am: WMD = 0.68 mmHg [0.15 to 1.21]; 12 pm: WMD = 0.90 mmHg [0.41 to 1.39]; 4 pm: WMD = 1.06 mmHg [0.61 to 1.51]). The incidence of hyperemia was significantly higher with BTFC than LTFC (pooled ORs: 1.85 [1.09 to 3.13]). The incidence of hyperemia was not significantly higher with TTFC than LTFC (pooled ORs: 2.52 [0.85 to 7.46]), and was not significantly higher with BTFC than TTFC (pooled OR: 1.65 [0.48 to 5.70])., Conclusions: BTFC provided significantly greater efficacy in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm than LTFC and TTFC. LTFC was as effective as TTFC in lowering IOP at the four measurement time points and BTFC caused conjunctival hyperemia in more patients than LTFC. Further clinical trials are needed because of the limited number of studies.

Background: To evaluate the safety and tolerability of Polyquad-preserved Travoprost (PQ-Travoprost) in patients previously treated with benzalkonium chloride (BAK)-preserved Latanoprost., Methods: Cohort 6-month study on open-angle glaucoma or ocular hypertension patients. Complete ophthalmic examination, intraocular pressure (IOP) measurement and ocular surface status (tear film break-up time [TF-BUT], corneal staining and ocular surface disease index [OSDI]) were evaluated at baseline and 6 months later., Results: A total of 44 patients were enrolled. Median (interquartile range [IQR]) baseline IOP was 18 (15.5 - 21) and 16 (14 - 17) mmHg (p < 0.0001) after 6 months. At baseline, 18 (40.9%) patients presented an IOP of < 18 mmHg, 11 (25%) < 16 mmHg, 2 (4.3%) < 14 mmHg and 1 (2.3%) < 12 mmHg; 6 months later the proportions were 36 (81.8%) (p < 0.0001), 21 (47.7%) (p = 0.00075), 8 (18.2%) (p = 0.0143) and 6 (13.6%) (p = 0.0253). Concerning safety, TF-BUT improved from 8 [IQR 6 - 10] to 10 [IQR 8 - 12] s (p < 0.0001). No eye developed corneal staining; punctate keratitis was absent in 13 (29.5%) patients at baseline and in 31 (70.4%) after 6 months (p < 0.001). OSDI changed from 16 (10 - 30) to 9 (2 - 20)., Conclusions: No patient treated with PQ-Travoprost developed ocular surface disease after 6 months of monotherapy, whereas many patients reached a good IOP control with lower IOP values. Ocular surface status statistically improved when examined by TF-BUT and corneal staining.

Purpose: To evaluate some clinically important features of benzalkonium chloride (BAK) toxicity by comparing tafluprost with 0.001% BAK and travoprost preserved with SofZia applied to the ocular surface of the eyes with glaucoma., Methods: This was a prospective, randomized, observer unmasked, multicenter crossover trial. A total of 195 patients were randomized and 174 patients completed the study at 19 clinics between November 2011 and August 2012. Topical BAK-preserved tafluprost or SofZia-preserved travoprost was newly administered or continued. Superficial punctate keratopathy (SPK), tear break-up time (BUT), the conjunctival hyperemia score, and intraocular pressure (IOP) were compared at the baseline visit, 4, and 12 weeks after the start of therapy. The eye drops were switched to another eye drop after 12 weeks of observation., Results: The total SPK and conjunctival hyperemia scores were significantly lower in the tafluprost compared with those in the travoprost phase (both P=0.038). There were no significant differences in the SPK scores of the superior area (P=0.679), central area (P=0.089), inferior area (P=0.090), and tear BUT (P=0.271). The IOP-lowering effects were similar (P=0.155)., Conclusions: SPK, hyperemia score, and tear BUT while using tafluprost with 0.001% BAK were not inferior compared with those caused by travoprost with SofZia.

Purpose: To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma., Methods: This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events., Results: The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student's t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements., Conclusions: Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.

Introduction: To compare the 24-h intraocular pressure (IOP) control and tolerability of travoprost/timolol benzalkonium chloride (BAK)-free (TTFC) vs. latanoprost/timolol fixed combination preserved with BAK (LTFC) in open-angle glaucoma patients insufficiently controlled with latanoprost 0.005% monotherapy given once in the evening., Methods: The authors have conducted a prospective, observer-masked, active-controlled, cross-over, comparison study. Qualified open-angle glaucoma patients who demonstrated a latanoprost-treated morning IOP (10:00 ± 1 h) greater than 20 mmHg on two separate visits were randomized for 3 months to receive either TTFC or LTFC. Patients were then crossed over to the opposite treatment for another 3 months. At the end of the latanoprost run-in and after each 3-month therapy period patients underwent 24-h IOP monitoring in the habitual position using Goldmann applanation tonometry in the sitting position during the day (10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the supine position at night (02:00 and 06:00). Selected ocular surface parameters were evaluated after each therapy period., Results: Forty-two open-angle glaucoma patients completed the study. The mean 24-h baseline IOP on latanoprost was 21.5 ± 1.6 mmHg. Both fixed combinations significantly reduced the IOP at each time point, for the mean, peak and fluctuation of 24-h IOP compared with latanoprost monotherapy (P < 0.01). When the two fixed combinations were compared directly, TTFC provided significantly lower mean 24-h IOP (18.9 ± 2.2 mmHg) vs. LTFC (19.3 ± 2.3 mmHg) (P = 0.004) and significantly lower IOP at 18:00 (18.6 ± 2.5 vs. 19.5 ± 2.7 mmHg for LTFC) (P < 0.001). Further, TTFC demonstrated significantly better tear film break-up time (5.15 vs. 4.65 s), corneal stain (1.5 vs. 1.8) and Schirmer I test (9.9 vs. 9.2 mm) compared with LTFC after 3 months of therapy (P < 0.01 for all comparisons)., Conclusion: The mean 24-h IOP lowering of TTFC was statistically more significant compared to LTFC in patients insufficiently controlled with latanoprost monotherapy. Measurement of ocular surface health and tear film status favored the BAK-free TTFC compared to LTFC.