Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. METHODS: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. RESULTS: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. CONCLUSION: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Primary Open-Angle Glaucoma Progression in Glaucoma Patients with Unchanged Topical Treatment over 3 Years - Retrospective Observational Cohort Analysis.

BACKGROUND: Lowering intraocular pressure (IOP) is a mainstay of glaucoma therapy. It is, however, still an open question whether a comparable level of long-term IOP lowering achieved by different medications results in comparable protection for the retinal ganglion cells. The purpose of this study was to retrospectively analyze glaucoma damage progression in two cohorts of primary open-angle glaucoma patients with different and unchanged therapy over a period of 3 years, and the main objective of this study was to determine possible differences in terms of structural [retinal nerve fiber layer thickness (RNFL)] and functional [visual field (VF)] outcome. PATIENTS AND METHODS: The retrospective observational cohort analysis compared two differently treated groups of glaucoma patients with their original, at study entry, topical therapy unchanged over 3 years. The main endpoint was the time course of RNFL thickness and VF mean defect (MD). RESULTS: Twenty-one eyes were included in each group. The first group (21 eyes) was on a fixed combination of timolol and dorzolamide twice a day and the second group on one drop of prostaglandin analog, either latanoprost alone (15 eyes) or travoprost alone (6 eyes), in an unchanged regimen over a period of 3 years. IOP in mmHg at baseline and at 36 months was 11.9 ± 2.4 and 13.0 ± 2.1 in the first, and 12.9 ± 3.0 and 14.1 ± 3.2 in the second group, respectively. RNFL thickness values in micrometers were at baseline and at 36 months 77.8 ± 12.3 and 76.6 ± 15.2 in the first, and 77.5 ± 15.2 and 72.8 ± 14.5 in the second group, respectively. VF MD in dB were 1.7 ± 2.5 and 1.2 ± 2.9 in the first, and 0.9 ± 2.3 and 0.7 ± 2.6 in the second group, respectively. CONCLUSION: Both groups had comparable baseline, as well as mean overall IOP. However, the course of IOP levels over time was different in the two groups, showing earlier and more pronounced long-term drift in the prostaglandin analog-treated group. RNFL thickness was comparable at baseline, however, RNFL thinning over time was more pronounced in the prostaglandin analog-treated group. There were no statistical differences between the groups in terms of VF MD at baseline and over time.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

Analysing the change in contrast sensitivity post-travoprost treatment in primary open-angle glaucoma patients using Spaeth Richman contrast sensitivity test.

OBJECTIVE: To determine the ability of the Internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) in assessing the change in contrast sensitivity (both central and peripheral) post-treatment with travoprost 0.004%. DESIGN: This is a prospective observational study. METHODS AND PARTICIPANTS: Data of 62 eyes (33 patients) undergoing treatment for naïve POAG patients were analysed. Patients were followed up for a period of six months after starting topical travoprost (Travatan 0.004%, Alcon), and the change in central and peripheral CS was studied. RESULTS: Mean total SPARCS score at baseline was 69 ± 10.99, improved to 74.62 ± 9.50 after 6 months of therapy (p: 0.001) in all the glaucoma severity groups. Mean SPARCS score at baseline in mild glaucoma group was 72.05 ± 9.87, in the moderate glaucoma group, it was 62.23 ± 9.2, and in the severe glaucoma group, it was 59.36 ± 11.65. After 6 months of treatment with travoprost, the CS improved to 76.05 ± 8.36 in mild group, 76.69 ± 8.82 in moderate group and 67.18 ± 11.15 in severe group (p value: 0.014). The percentage change in the CS from baseline showed significant improvement in the superotemporal quadrant at 1 month (p value: 0.032), superonasal quadrant (p value: 0.049), inferotemporal quadrant at 3 months (p value: 0.003) and 6 months (p value: 0.039). Inferonasal quadrant was affected most by glaucoma. A statistically significant correlation was seen between total SPARCS score with MD and PSD. Correlation was also seen between the percentage change in CS and average RNFL thickness at 3 and 6 months. CONCLUSION: Both central and peripheral CS improve following IOP reduction with travoprost. Change in the CS has a significant correlation with RNFL thickness and the perimetric indices.

Switching to Preservative-Free Tafluprost/Timolol Fixed-Dose Combination in the Treatment of Open-Angle Glaucoma or Ocular Hypertension: Subanalysis of Data from the VISIONARY Study According to Baseline Monotherapy Treatment.

INTRODUCTION: The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy. METHODS: A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6. RESULTS: The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7  (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001). CONCLUSION: PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively. CLINICAL STUDY NUMBER: European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.

Duración del efecto hipotensor de los análogos de prostaglandinas medido con la prueba de sobrecarga hídrica en pacientes con glaucoma / Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients

Objetivo Medir con la prueba de sobrecarga hídrica (PSH) la magnitud y duración del efecto hipotensor de dos análogos de prostaglandinas en pacientes con glaucoma. Métodos Los pacientes recibieron latanoprost o travoprost cada 24 horas y luego cada 48 horas. Se practicaron PSH sin tratamiento a las 7 am y con tratamiento 12, 36 y 44 horas después de la última dosis; se calcularon el pico de presión intraocular (PIO), la fluctuación y la diferencia entre el pico y las medidas aisladas de PIO en horas de consulta. Resultados Se incluyeron 41 ojos de 21 pacientes con glaucoma primario de ángulo abierto, 22 ojos recibieron latanoprost y 19, travoprost. La PIO aislada promedio sin tratamiento fue 17,20 desviación estándar (D.S.) 3,73 y 16,95 D.S. 2,61mmHg y el pico de presión 22,45 D.S. 2,91 y 21,58 D.S. 3,79mmHg, para los grupos de latanoprost y travoprost, respectivamente. Con tratamiento, la presión pico se redujo en 22,64% y 20,29% a las 12 horas, 18,44% y 14,64% a las 36 horas y 16,17% y 14,46% a las 44 horas, respectivamente. La fluctuación sin tratamiento fue 4,36 y 5,11mmHg, y con tratamiento a las 12 horas se redujo a 2,77 y 2,89mmHg, aumentando nuevamente a 36 y 44 horas. Conclusiones Se evidenció un efecto hipotensor hasta 44 horas después de la última dosis de latanoprost y travoprost, similar para los dos medicamentos y decreciente en el tiempo. La fluctuación de la PIO sólo se redujo a las 12 horas (AU)

Objective To measure the magnitude and duration of the hypotensive effect of two prostaglandin analogues in glaucoma patients using the water drinking test (WDT). Methods Patients received latanoprost or travoprost every 24hours and then every 48hours. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44hours after the last dose; intraocular pressure (IOP) peak, fluctuation and the difference between peak and isolated IOP measurements at consultation times were calculated. Results Forty-one eyes of 21 patients with primary open-angle glaucoma were included; 22 eyes received latanoprost, and 19 received travoprost. Mean untreated isolated IOP was 17.20 standard deviation (S.D.) 3.73 and 16.95 S.D. 2.61mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12hours, 18.44% and 14.64% at 36hours and 16.17% and 14.46% at 44hours, respectively. The fluctuation without treatment was 4.36 and 5.11mmHg, and with treatment at 12hours was reduced to 2.77 and 2.89mmHg, increasing again at 36 and 44hours. Conclusions A hypotensive effect was evident up to 44hours after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12hours (AU)

Short-term efficacy of latanoprostene bunod for the treatment of open-angle glaucoma and ocular hypertension: a systematic literature review and a network meta-analysis.

BACKGROUND/AIMS: To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP). METHODS: A systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated. RESULTS: A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%. CONCLUSION: LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension.

PURPOSE: To evaluate the additive intraocular pressure-lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) as an adjunct to a prostaglandin analog (PGA) in patients with open-angle glaucoma or ocular hypertension insufficiently controlled with PGA monotherapy. METHODS: In this Phase 4, double-masked trial, patients aged ⩾18 years, with a mean intraocular pressure of ⩾19 and <32 mm Hg in at least one eye were randomized (1:1) to receive BBFC + PGA (n = 96) or vehicle + PGA (n = 92) for 6 weeks. The primary endpoint was the mean change in diurnal intraocular pressure from baseline (averaged over 09:00 and 11:00 h) at Week 6. RESULTS: The mean diurnal intraocular pressure at baseline was similar in the BBFC + PGA (22.8 mm Hg) and vehicle + PGA (22.9 mm Hg) groups. The least squares mean change in diurnal intraocular pressure from baseline at Week 6 was greater with BBFC + PGA (-5.59 mm Hg (95% confidence interval: -6.2 to -5.0)) than with vehicle + PGA (-2.15 mm Hg (95% confidence interval: -2.7 to -1.6)); the treatment difference was statistically significant in favor of BBFC + PGA (-3.44 mm Hg, (95% confidence interval: -4.2 to -2.7); p < 0.001). Ocular adverse events were reported in 21.1% and 8.7% of patients in the BBFC + PGA and vehicle + PGA groups, respectively. The most frequent ocular adverse event was ocular hyperemia (5.3%) in the BBFC + PGA group and blurred vision (2.2%) in the vehicle + PGA group. CONCLUSION: BBFC + PGA significantly reduced mean diurnal intraocular pressure than PGA alone in patients with open-angle glaucoma or ocular hypertension. The safety findings with BBFC + PGA were consistent with the known safety profile of the individual medications.

Effectiveness of Blepharoptosis Surgery in Patients With Deepening of the Upper Eyelid Sulcus.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ±â€Š0.96 mm before surgery and 3.72 ±â€Š0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Correlation of Ocular Surface Disease and Quality of Life in Indian Glaucoma Patients: BAC-preserved versus BAC-free Travoprost.

Objectives: The use of benzalkonium chloride (BAC)-preserved medications is associated with ocular surface disease (OSD) that can negatively affect quality of life (QoL) in glaucoma patients. This study aimed to compare QoL and correlate it with OSD in glaucoma patients receiving BAC-preserved and BAC-free travoprost. Materials and Methods: A total of 110 subjects were divided into 3 groups: 40 primary open-angle glaucoma (POAG) patients using BAC-preserved travoprost, 40 POAG patients using BAC-free travoprost, and 30 age-matched controls. All patients were assessed using a single interviewer-administered format of the Ocular Surface Disease index (OSDI) and Glaucoma Quality of Life-15 (GQL-15) questionnaires. Results: Mean GQL-15 score in the BAC group was significantly higher than in the BAC-free group (24.71±7.42 vs. 17.58±3.06; p<0.05). The mean difference in GQL-15 scores between controls and the BAC-free group (1.24) was insignificant (p>0.05). There was a strong positive correlation between OSDI scores and GQL-15 scores in all the groups (r values: BAC: 0.63, BAC-free: 0.23, controls: 0.29), with higher OSDI scores (severe OSD) associated with higher GQL-15 scores (worse QoL). Cronbach's alpha was 0.84 for GQL-15 and 0.75 for OSDI. Conclusion: BAC-preserved travoprost leads to higher OSDI scores, which correlate strongly with poor QoL scores as compared to BAC-free travoprost. The use of BAC-free formulations should be encouraged to reduce the onset or worsening of OSD and impaired QoL in glaucoma patients.

Changes in Prostaglandin-associated Periorbital Syndrome After Switch from Conventional Prostaglandin F2α Treatment to Omidenepag Isopropyl in 11 Consecutive Patients.

PURPOSE: We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl. PATIENTS AND METHODS: From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation. RESULTS: The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost. CONCLUSIONS: Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.

Effect of 6-week washout period on intraocular pressure following chronic prostaglandin analogue treatment: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of a 6-week washout period on intraocular pressure (IOP) following long-term monotherapy prostaglandin use. DESIGN: Prospective, randomized, controlled, single-centre, single-blinded, parallel-group clinical study. PARTICIPANTS: Subjects aged >18 years diagnosed with open-angle glaucoma or open-angle glaucoma suspects based on elevated IOP in one or both eyes, using monotherapy topical latanoprost, bimatoprost, or travoprost once daily. METHODS: Subjects were prospectively randomized to continue prostaglandin analogue (PGA) monotherapy (control group) or discontinue PGA monotherapy (washout group) for 42 days. IOP was measured at day 0 (day of randomization), 7, 21, and 42. MAIN OUTCOME MEASURE: Mean IOP (mm Hg) ± standard deviation. RESULTS: 154 eyes (87 participants) completed the study, with 69 eyes (39 participants) in the control group and 85 eyes (48 participants) in the washout group. In the control group, day 0 IOP (14.64 ± 2.68 mm Hg) did not significantly differ from IOP at days 7 (14.25 ± 3.01 mm Hg), 21 (14.57 ± 2.61 mm Hg), and 42 (14.78 ± 2.30 mm Hg) (all p > 0.30). In the washout group, mean IOP values at days 7 (16.19 ± 3.80 mm Hg), 21 (17.28 ± 3.55 mm Hg), and 42 (17.84 ± 3.31 mm Hg) were significantly greater than those at day 0 (14.48 ± 1.94 mm Hg) and day-matched control group values (all p < 0.002). In the washout group, 24.7% of eyes had a day 42 IOP ≥21 mm Hg. No eyes in the control group had a day 42 IOP ≥21 mm Hg. CONCLUSIONS: Six weeks of PGA washout after long-term monotherapy resulted in a small but statistically significant IOP increase. Majority of washout group participants maintained an IOP lower than 21 mm Hg after the 6-week washout duration. (https://clinicaltrials.gov/ identifier, NCT03534882).

Decreasing intraocular pressure significantly improves retinal vessel density, cytoarchitecture and visual function in rodent oxygen induced retinopathy.

We attempted to explore a noninvasive, easily applicable and economically affordable therapy for retinopathy of prematurity (ROP). Rat pups were raised in 80% oxygen from postnatal day 7 to P12, and returned to room air. Travoprost eye drops were administered twice a day for 7 days, to reduce intraocular pressure (IOP) by about 20%. Immunohistochemical staining was performed to visualize vessel endothelial cells, to analyze retinal neurons and cytoarchitecture. Behavioral experiments were carried out to test visual acuity and contrast sensitivity. At the end of the 7-day treatment, the number of vessels extending to the vitreous body was significantly reduced and retinal vessel density increased. This improvement was maintained to the end of the 12th week. In the central retina of the model group, the horizontal cells were completely wiped out, the outer plexiform layer was undetectable, and the rod bipolar cell dendrites sprouted into the outer nuclear layer. The treatment partially reverted these architectural changes. Most importantly, behavioral experiments revealed significantly improved visual acuity and contrast sensitivity in the treated group. Therefore, reducing IOP could potentially serve as a safe and economical measure to treat ROP.

Efficacy And Safety Of Travoprost Versus Timolol To Treat Early-Onset Ocular Hypertension Secondary To Vitrectomy: A Randomized Trial.

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.

Evaluation of Contrast Sensitivity after Four Different Treatment Modalities Using OPTEC-Functional Vision Analyzer in Primary Open-Angle Glaucoma.

PURPOSE: The purpose of the study is to evaluate the changes in contrast sensitivity (CS) after using the four different types of antiglaucoma eye drops in patients with primary open-angle glaucoma (POAG) by OPTEC-functional vision analyzer (FVA). METHODS: In this prospective study, eighty patients (80 eyes) with POAG were randomly divided into four groups. The groups were randomly received timolol maleate 0.5%, travoprost 0.004%, dorzolamide 2%, and brimonidine tartrate 0.2%. The medications were used in the eye that was randomly selected. The CS was assessed before and 15 min after the intervention by the FVA. The paired t-test was used to compare the difference between before and after the intervention. P < 0.05 was considered statistically significant. RESULTS: Fifteen minutes after the instillation of timolol maleate (Group A), the CS in three out of twenty patients at the spatial frequencies of 1.5, and 3 cycles per degree (cpd) was significantly decreased (P = 0.015). However, using travoprost (Group B) and dorzolamide (Group C), the CS in one out of twenty patients at low spatial frequencies (1.5 and 3 cpd) was decreased in the two groups, which was not statistically significant for these medications (P > 0.05). In Group D, after applying brimonidine tartrate, the CS in two out of twenty patients at the spatial frequency of 18 cpd was significantly decreased (P = 0.042). CONCLUSION: Our study showed that CS values at low and high spatial frequencies after applying timolol and brimonidine eye drops are temporarily reduced in patients with POAG.

Efficacy of travoprost for the treatment of patients with glaucoma.

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.

Efficacy and safety of prostaglandin analogues in primary open-angle glaucoma or ocular hypertension patients: A meta-analysis.

BACKGROUND: To evaluated and compared the efficacy and safety of 3 prostaglandin analogues (0.005% latanoprost, 0.004% travoprost, and 0.03% bimatoprost) in treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: PubMed, Embase, Cochrane library, Web of science, CNKI, Wanfang, and Vip database, published between January 1, 2000 and June 1, 2018, were systematically examined for randomized controlled trials (RCT) based on prostaglandin analogues for POAG or OHT treatment. Statistical analyses including weighted mean difference (WMD) calculation and odds ratio (OR) were performed using Review Manager Software version 5.3. RESULT: The 17 studies were included in this analysis (N = 2433 participants) with 1∼12 months' follow-ups. The difference of intraocular pressure (IOP) reduction between latanoprost and travoprost group had not significant; there was significant difference of IOP reduction between latanoprost and bimatoprost group in the third month and sixth month; Travoprost was significantly different from bimatoprost in reducing IOP in the third month. Travoprost revealed an elevated risk of conjunctival hyperemia compared with latanoprost. An elevated risk of conjunctival hyperemia and growth of lashes compared with latanoprost. Bimatoprost shows lower ocular tolerability with higher incidence of side effects such as conjunctival hyperemia. CONCLUSIONS: 0.03% bimatoprost appears more effective following long time use (3 and 6 month post-treatment) for IOP control compared to 0.005% latanoprost, and is more effective compared to 0.004% travoprost after being used for a certain period of time (3 months post-treatment); nevertheless, 0.005% latanoprost is better tolerated in patients with POAG or OHT.

Prospective randomized clinical trial on the effects of latanoprost, travoprost and bimatoprost on latanoprost non-responders.

PURPOSE: To determine whether a patient who is non-responder to latanoprost after one month of use should continue using latanoprost or switch to either bimatoprost or travoprost. PATIENTS AND METHODS: Prospective randomized clinical trial. We recruited new patients who were felt to require intraocular pressure reduction. Patients who had≤20% intraocular pressure reduction after one month of latanoprost treatment were randomly assigned to another month of treatment with latanoprost or a switch to bimatoprost or travoprost for an additional month. RESULTS: Overall, 83 non-responders to latanoprost after one month of treatment were included in the study. Before latanoprost treatment, the mean intraocular pressure was 23.7±4.7mmHg. At randomization on latanoprost, mean intraocular pressure was 21.5±4.5mmHg. One month after the switch of medication, the mean reduction in intraocular pressure was not significantly different between the groups (P=0.148) and was -0.9mmHg, -2.10mmHg and -2.5mmHg, for latanoprost, bimatoprost and travoprost respectively. One month after randomization, 32 (38.5%) of the patients had become responders, with IOP reduction>20%. Of those patients, 9 (31%) were using latanoprost, 13 (41.9%) bimatoprost and 10 (43.5%) travoprost. The number of new responders was similar between the three groups (P=0.584). CONCLUSION: There is no added benefit of switching latanoprost to another topical prostaglandin for patients who are initially non-responders. Regression towards the mean and the Hawthorne effect are probably important factors explaining the additional IOP reduction obtained after randomization and explain the result of most switch studies.

An in vivo confocal, prospective, masked, 36 months study on glaucoma patients medically treated with preservative-free or preserved monotherapy.

The aim of this study was to evaluate the in vivo effects at 3 years of preservative-free tafluprost on corneal health. It was a prospective, masked, study on consecutive patients with a new prescription of preservative-free (PF) tafluprost (naïve-N or switched-S, 44 and 14 patients), and preserved (P) bimatoprost 0.003% or travoprost 0.004% (P-group, 35 patients). A complete ophthalmic examination and an in vivo corneal confocal microscopy evaluation were performed at baseline and every 6 months for 3 years. Ninety-three patients were enrolled, clinical parameters were similar in the groups at baseline, apart from intraocular pressure (IOP) which was lower in the S-group (p = 0.012). Both at baseline and over time, confocal microscopy parameters had different trends. At baseline, keratocyte activation was similar in the three groups (p = 0.43) but over the next months naïve patients treated with PF-tafluprost presented a significant (p = 0.004) reduction in keratocyte activation. Sub-basal nerves tended to increase in patients switched to PF-tafluprost (p = 0.07) while were stable in the other two groups (p = 0.11 in PF and 0.40 in P group). Grade of tortuosity was stable over time in the three groups. Beading-like formations were stable over time for the P- and the PF-group, while significantly increased in the S-group (p = 0.027). Endothelial density values were statistically different at baseline (p = 0.007), they decreased both in PF-group and in S-group (p = 0.048 and 0.001, respectively), while increased in P-group (p = 0.006). Our study is the first to show that a PF-tafluprost formulation does not significantly alter the corneal structures as examined by confocal microscopy after 36 months of topical daily therapy, while improving corneal alterations due to chronic preserved therapies.

Patient Preference-Based Comparative Effectiveness and Cost-Utility Analysis of the Prostamides for Open-Angle Glaucoma.

PURPOSE: To perform patient preference-based comparative effectiveness and cost-utility (cost-effectiveness) analyses to evaluate topical bimatoprost 0.01%, latanoprost 0.005%, travoprost 0.004%, tafluprost 0.0015%, and timolol 0.5% for the treatment of open-angle glaucoma (OAG). METHODS: Value-Based Medicine®, incremental cost-utility analysis, and average cost-utility analysis were performed using published systematic review and network meta-analyses with 3-month clinical data for a base case of OAG with an untreated intraocular pressure of 26 mm Hg. Visual acuity and visual field changes were converted to time tradeoff utility format. A 20-year model was undertaken; bilateral therapy was presumed; a national average Medicare Fee Schedule was used; and ophthalmic, third party insurer, and societal cost perspectives were utilized. Patient value outcomes (QALYs or quality-adjusted life-years) and costs were discounted at 3% annually. RESULTS: Bimatoprost conferred a mean 2.56 QALY gain (22.9% patient quality-of-life gain) for the average OAG patient, while latanoprost for the average OAG patient, while latanoprost conferred a 2.00 QALY gain (17.8% quality-of-life gain), tafluprost a 1.99 QALY gain (17.9% quality-of-life gain), travoprost a l.92 QALY gain (17.2% quality-of-life gain), and timolol a 1.42 QALY gain (12.8% quality-of-life gain). The ophthalmic cost-perspective, incremental cost-utility ratio of bimatoprost referent to travoprost was $6,034/QALY, to latanoprost was $27,973/QALY, and to timolol was $16,063/QALY. Bimatoprost dominated tafluprost, meaning that it conferred greater patient value for lesser cost than tafluprost. CONCLUSIONS: Topical bimatoprost delivers greater patient value than the other prostamides and topical timolol for the treatment of OAG. Bimatoprost is incrementally cost-effective referent to the other prostamides and timolol.