A latanoprost cationic emulsion (STN1013001) vs. other latanoprost formulations (Latanoprost) in open angle glaucoma/ocular hypertension and ocular surface disease: an Italian cost-utility analysis.

BACKGROUND: STN1013001 is an innovative latanoprost cationic emulsion for open-angle glaucoma/ocular hypertension (OAG/OHT) and ocular surface disease (OSD). METHODS AND FINDINGS: A 5-year, 7 health states, 1-year cycle early Markov model-supported cost-utility analysis (CUA) of STN1013001 vs. other latanoprost formulations (Latanoprost) followed the Italian National Health Service (INHS) perspective.One-way, probabilistic and scenario sensitivity analyses tested the uncertainty of the baseline results. Value of information analysis (VOIA) investigated the potential cost-effectiveness of collecting further evidence. RESULTS: Over 5 years, the Markov model-supported CUA predicts STN1013001 to be potentially highly cost-effective vs. Latanoprost (+€57.60 cost at €2020 values; +0.089 Quality-Adjusted Life Years).The Incremental Cost-Utility Ratio (€647.65) falls well below the lower limit of the acceptability range proposed for Italy (€25,000-€40,000).Sensitivity analyses confirmed the robustness of the baseline findings. VOIA highlighted that further information might only be cost-effective for OAG/OHT utilities and OSD-related disutility. CONCLUSION: STN1013001 is potentially highly cost-effective and strongly dominant vs. Latanoprost for OAG/OHT+OSD patients from the INHS perspective. These findings should be re-assessed using the data from the ongoing Phase III trial (NCT04133311) comparing the efficacy and safety of STN1013001 vs. Latanoprost and with future real-world CUAs upon the availability of STN1013001 on the Italian market.

Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial.

Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

Assessment of ocular surface disease in glaucoma patients with benzalkonium chloride-preserved latanoprost eye drops: a short-term longitudinal study.

PURPOSE: To prospectively evaluate the effect of benzalkonium chloride (BAK)-preserved latanoprost on ocular surface damage and identify the associated risk factors among treatment-naive glaucoma patients. METHODS: The basal Schirmer's test results, corneal Oxford staining score, non-invasive keratograph tear-breakup time, oculus hyperemia index score (objective metrics), and ocular surface disease index (OSDI) questionnaire (subjective metric) were evaluated at baseline, 1 month, and 4 months after receiving latanoprost eye drops. Associated risk factors were assessed by multivariate linear regression. RESULTS: Seventy-four eyes (44 patients) were enrolled. Basal Schirmer's test tear-flow and Oxford scores gradually deteriorated (ß = -0.14, P = 0.001 and ß = 0.1, P < 0.001, respectively). The percentage of unstable tear-film (breakup time < 10 s) increased significantly at 4 months (6.21% vs 9.11%, P = 0.042). Hyperemic scores increased significantly at 1 month and normalized at 4 months (P = 0.01 and P = 0.16, respectively); total OSDI scores tended to improve (ß = -0.76, P = 0.06). Older age was associated with additional corneal Oxford staining (P = 0.005); female sex was associated with increased unstable tear-film scores (P = 0.01). Artificial tear use was associated with a smaller decrease in basal Schirmer's test values (P = 0.01) and a smaller increase in unstable tear-film scores (P = 0.02). CONCLUSIONS: Preserved latanoprost eye drops affected ocular surface changes in glaucoma patients through decreased basal tear secretion. Artificial tears represent an early intervention in vulnerable glaucoma patients with reduced tear secretion and impaired tear-film stability.

Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study.

BACKGROUND/AIMS: Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops. METHODS: A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways. RESULTS: Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation. CONCLUSIONS: The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption. TRIAL REGISTRATION NUMBER: ISRCTNID:ISRCTN75888393.

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.

A Worldwide Price Comparison of Glaucoma Medications, Laser Trabeculoplasty, and Trabeculectomy Surgery.

Importance: Medical and surgical interventions for glaucoma are effective only if they are affordable to patients. Little is known about how affordable glaucoma interventions are in developing and developed countries. Objective: To compare the prices of topical glaucoma medications, laser trabeculoplasty, and trabeculectomy relative with median annual household income (MA-HHI) for countries worldwide. Design, Setting and Participants: Cross-sectional observational study. For each country, we obtained prices for glaucoma medications, laser trabeculoplasty, and trabeculectomy using government pricing data, drug databases, physician fee schedules, academic publications, and communications with local ophthalmologists. Prices were adjusted for purchasing power parity and inflation to 2016 US dollars, and annual therapy prices were examined relative to the MA-HHI. Interventions costing less than 2.5% of the MA-HHI were considered affordable. Main Outcomes and Measures: Daily cost for topical glaucoma medications, cost of annual therapy with glaucoma medications, laser trabeculoplasty, and trabeculectomy relative to MA-HHI in each country. Results: Data were obtained from 38 countries, including 17 developed countries and 21 developing countries, as classified by the World Economic Outlook. We observed considerable variability in intervention prices compared with MA-HHI across the countries and across interventions, ranging from 0.1% to 5% of MA-HHI for timolol, 0.1% to 27% for latanoprost, 0.2% to 17% for laser trabeculoplasty, and 0.3% to 42% for trabeculectomy. Timolol was the most affordable medication in all countries studied and was 2.5% or more of MA-HHI in only 2 countries (5%). The annual cost of latanoprost was 2.5% or more of MA-HHI in 15 countries (41%) (15 developing countries [75%] and no developed countries). The cost of laser trabeculoplasty was 2.5% or more of the MA-HHI in 15 countries (44%) (11 developing countries [65%] and 4 developed countries [24%]). The cost of trabeculectomy was 2.5% or more of the MA-HHI in 28 countries (78%) (18 developing countries [95%] and 10 developed countries [59%]). In 18 countries (53%), laser trabeculoplasty cost less than a 3-year latanoprost supply. Conclusions and Relevance: For many patients worldwide, the costs of medical, laser, and incisional surgical interventions were 2.5% or more of the MA-HHI. Successfully reducing global blindness from glaucoma requires addressing multiple contributing factors, including making glaucoma interventions more affordable.

Prospective study comparing Xalatan® eye drops and two similar generics as to the efficacy and safety profile.

PURPOSE: To evaluate the efficacy and safety between two generic prostaglandins Lataz-Xalaprost (Greece) and the corresponding original drops (Xalatan®). MATERIAL AND METHODS: In this prospective randomized study, 60 patients diagnosed with open-angle glaucoma or ocular hypertension were enrolled, who had never received antiglaucoma treatment. Subjects were divided randomly into three groups (Xalatan, Lataz, and Xalaprost groups) and they were studied over 16 weeks. At each visit, the mean applanation tonometry values and tear break-up time were measured. The Ocular Surface Disease Index questionnaire was used to evaluate patient's symptoms. RESULTS: There was a statistically significant difference (p < 0.001) in the mean values of the intraocular pressure between the baseline and the last visit (Xalatan group: from 23.11 ± 1.61 mmHg to 15.81 ± 1.22 mmHg, Lataz group: from 23.26 ± 1.33 mmHg to 15.80 ± 1.47 mmHg, and Xalaprost group: from 23.08 ± 1.45 mmHg to 16.08 ± 1.38 mmHg). Both generic eye drops showed mean percentage intraocular pressure reduction comparable to the standards of prostaglandin analogues (Xalatan: 31.57%, Lataz: 32.06%, and Xalaprost: 30.34%). Xalatan reduced the tear break-up time less, followed by Lataz and then by Xalaprost (Xalatan: from 8.5 to 8 s, Lataz: from 8.2 to 7.4 s, and Xalaprost: from 8.7 to 7.7 s). Xalatan presented the best safety profile, followed by Lataz and least was Xalaprost, according to Ocular Surface Disease Index questionnaire's results. CONCLUSION: No significant difference was recorded in the effectiveness of each generic prostaglandin compared to the original. Furthermore, no patient had to change medication. The differences that arose in the safety profile of the three eye drops suggest a prompt closer initial monitoring of patients who are administered generic eye drops.

Periorbital Changes associated with Topical Prostaglandins Analogues in a Hispanic Population.

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.

Assessment of the Anterior Chamber Flare and Macular Thickness in Patients Treated with Topical Antiglaucomatous Drugs.

PURPOSE: To determine the changes in the anterior chamber flare and central macular thickness (CMT) under topical antiglaucomatous therapy. METHODS: This study included 121 eyes of 73 patients and 36 eyes of 18 controls. Glaucoma patients were divided into 3 groups (timolol maleate, latanoprost, and bimatoprost). Control eyes did not receive any medications. Flare and CMT measurements were performed at baseline and follow-up visits (15th day, and 1st, 3rd, 6th, and 12th month). RESULTS: Statistically significant increases were detected in the flare values in the bimatoprost and latanoprost groups (P < 0.001, P = 0.011, respectively). Significant increases were also found in CMT values measured in these 2 groups (P < 0.001, P = 0.002, respectively). However, increased flare and CMT values were not clinically manifested as uveitis and macular edema. Flare and CMT values did not change statistically in the timolol maleate and control groups. CONCLUSIONS: Although the use of prostaglandin (PG) analogs was found to be associated with increased flare and CMT, these increases were not clinically significant. PG analog monotherapy may be safely and effectively used in the treatment of glaucoma.

The physical properties of generic latanoprost ophthalmic solutions are not identical.

PURPOSE: To compare various characteristics of Xalatan® and five generic latanoprost ophthalmic solutions. METHODS: Drop size, volume, pH values, buffer capacity, viscosity, hardness of bottles and costs were determined. Drop sizes were measured in triplicates by micropipettes, and the number of drops counted in three separate bottles of each generic product was determined. pH values were measured in triplicates by a calibrated pH meter. Buffer capacity was exploited by titrating known quantities of strong base into 2.5 ml of each brand and interpolated to neutral pH. Kinematic viscosity was determined by linear regression of timed gravity flow from a vertical syringe through a 21-G cannula. The hardness of the bottles was evaluated by gradually increasing tension on a hook placed around each bottle until a drop was expelled reading the tension on an attached spring scale. RESULTS: Drop sizes and the number of drops in the bottles varied significantly between the generic drugs. The control value of pH in the brand version (Xalatan® ) was markedly lower compared to the generic latanoprost products. Titration of Xalatan® to neutrality required substantially more NaOH compared to the generic latanoprost products. Finally, the viscosity revealed a significant variability between brands. Remarkable differences were found in bottle shapes, bottle hardness and costs of the latanoprost generics. CONCLUSION: Generic latanoprost eye drops should not be considered identical to the original brand version as regards to drop size, volumes, pH values, buffer capacity, viscosity, hardness of bottles and costs. It is likely that these issues affect compliance and intraocular pressure (IOP)-lowering effect. Therefore, re-evaluation of the requirements for introducing generic eye drops seems reasonable.

Variation in Number of Doses, Bottle Volume, and Calculated Yearly Cost of Generic and Branded Latanoprost for Glaucoma.

PURPOSE: To evaluate discrepancies in doses per bottle, bottle fill volume, and cost among branded and generic formulations of latanoprost. DESIGN: Comparative economic analysis. METHODS: This study was conducted at the Ruiz Department of Ophthalmology and Visual Science at The University of Texas Health Science Center at Houston (UTHealth). Four regionally available latanoprost formulations were measured. Number of drops per bottle and actual bottle fill volume were measured for a calculated sample size (10 bottles). Annual cost (using average wholesale price), days use per bottle, drops per milliliter, and number of bottles used per year were calculated. Data were summarized using mean and standard deviation; 1-way analysis of variance and post hoc Tukey's studentized range test were used for comparing means among manufacturers. RESULTS: Pfizer's branded lantanoprost, Xalatan (New York, New York, USA), had the largest fill volume (P < .001). Pfizer had the highest yearly cost at $1198 (P < .001), whereas Akorn (Lake Forest, Illinois, USA) and Bausch & Lomb (Rochester, New York, USA) had the lowest ($184 and $201, respectively). Pfizer and Bausch & Lomb had the most drops per bottle (87.3 and 88.7, respectively), which was statistically more (P < .001) than either Akorn or Sandoz (Princeton, New Jersey, USA) (77.6 and 76.6, respectively), but there was no statistical difference among the standard deviation of drops per bottle (Levene 0.14). CONCLUSIONS: Annual cost and number of doses per bottle, factors important to patients, vary significantly depending on the manufacturer of latanoprost. Practitioners can better advise patients by being aware of these differences.

Impact of the introduction of generic latanoprost on glaucoma medication adherence.

PURPOSE: To assess possible changes in medication adherence to prostaglandin analog (PGA) regimens among patients with open-angle glaucoma (OAG) after the initial introduction of generic PGAs. DESIGN: Longitudinal cohort analysis. PARTICIPANTS: Patients older than 40 years with OAG continuously enrolled in a nationwide managed-care network during 2009-2012 who used PGAs. METHODS: Mean adherence rates were calculated for topical PGA use during the 18 months before the introduction of generic latanoprost (September 2009-February 2011) and the 18 months after generic latanoprost became available (July 2011-December 2012). The rates were compared between persons who continued to use brand-name PGAs once generic latanoprost became available and others who switched to generic latanoprost. Multivariable logistic regression identified variables associated with an improvement or worsening of adherence of ≥25%. MAIN OUTCOME MEASURES: Mean adherence rates and odds of 25% or more improved or worsened adherence (with 95% confidence intervals [CIs]). RESULTS: A total of 8427 patients met the study eligibility criteria. Compared with persons switching to generic latanoprost, patients who continued taking brand name PGAs were 28% less likely to have improved adherence (odds ratio [OR], 0.72; 95% CI, 0.55-0.94) and 39% more likely to have reduced adherence (OR, 1.39; 1.04-1.86) of ≥25%. Improved adherence after the generic drug's introduction was also associated with higher monthly medication copay in the pregeneric period (P = 0.02), lower copay after introduction of the generic drug (P < 0.0001), and black race (OR, 1.25; 95% CI, 1.04-1.50). Six-hundred twelve patients (7.3%) discontinued all antiglaucoma interventions when generic latanoprost became available. CONCLUSIONS: Given that cost can significantly deter adherence, switching patients to generic medications may help improve patients' drug-regimen adherence. A considerable number of patients discontinued glaucoma drug use altogether when generic latanoprost became available. Ophthalmologists should work with insurers and pharmacists to prevent such discontinuation of use as generic forms of other PGA agents become available.

A study of the association between patterns of eye drop prescription and medication usage in glaucoma subjects.

PURPOSE: To investigate the association between patterns of eye drop prescription and medication usage in patients with glaucoma. PATIENTS AND METHODS: Sixty-seven Japanese patients with glaucoma who were prescribed topical antiglaucoma medications including a prostaglandin analogue bilaterally for >6 months at Nayoro City General Hospital, Nayoro, Japan, were included in the study. A self-administered, 5-item patient questionnaire was administered to determine how patients routinely use medications, including the method of eye drop administration, number of eye drops per instillation, accuracy of eye drop placement, weekly frequency of eye drop application, and their awareness of local side effects. The number of prostaglandin analogue bottles prescribed monthly was compared in each factor. RESULTS: The mean patient age was 74.4±10.0 years (range, 52 to 95 y; 39 women, 28 men). The mean duration of glaucoma treatment was 4.2±3.2 years (range, 0.7 to 10.6 y). Patients who placed the eye drops outside the eye were prescribed significantly more bottles monthly (P=0.008). The other factors had no significant effect on the number of bottles prescribed monthly. CONCLUSIONS: Patients with glaucoma who used eye drops incorrectly were routinely prescribed additional bottles of eye drops. Ophthalmologists should determine whether patients who request an unusual number of eye drops are using the eye drops correctly.

Original and generic latanoprost for the treatment of glaucoma and ocular hypertension: are they really the same?

We compared the intraocular pressure (IOP)-lowering effect and safety profile of latanoprost (Xalatan) with its generic variant, Glautan (Unipharm, Tel Aviv, Israel). After 1 and 4 weeks of treatment, a randomized, prospective, cross-over comparison was carried out that included patients with open-angle glaucoma or ocular hypertension, either naïve or treated and well-controlled, who were attending the Department of Ophthalmology, Tel Aviv Medical Centre, Tel Aviv, Israel, between May 2010 and November 2012. After a 3-week washout period for the medicated subjects, the participants were randomized to 4 weeks of treatment with either Xalatan or Glautan once every evening and then, after a 3-week washout period, crossed-over to the other treatment for an additional 4 weeks. Efficacy was expressed by a change in intraocular pressure at three designated hours of the day after 1 week and 1 month of treatment, and tolerability was determined by ocular side-effects as reported by the patient in a questionnaire. A total of 19 patients (mean age at initial diagnosis 66 ± 9 years, 14 females) were enrolled, of whom 17 had bilateral open-angle glaucoma and two had unilateral disease. Both drugs lowered intraocular pressure after 1 week and 1 month (P = 0.06 and P = 0.04, respectively) of treatment. Xalatan had a tendency of greater efficacy than Glautan both after 1 week and 1 month, but the difference was not statistically significant (P = 0.69 and P = 0.34, respectively). Drug safety was similar for Xalatan or Glautan, but more ocular side-effects were reported after treatment with Glautan (21 vs 12 for Xalatan, P = 0.06).

Safety assessment of subconjunctivally implanted devices containing latanoprost in Dutch-belted rabbits.

PURPOSE: Latanoprost is used for the treatment of an increased intraocular pressure (IOP) to prevent the progression of glaucoma. Since the lack of compliance with topical ocular dosing may compromise efficacy, alternate methods of delivery are being sought. A 9-month study was conducted to assess the safety and tolerability of latanoprost-containing subconjunctivally implanted devices. METHODS: Dutch-belted rabbits were implanted subconjunctivally with up to 5 placebo or drug-loaded devices containing from 50 to 180 µg of latanoprost per device. Study assessment consisted of irritation scoring, clinical signs, ophthalmic exams, IOP, electroretinography (ERG), ocular histology of cohorts at 3 and 9 months postimplantation, and systemic exposure to latanoprost acid. RESULTS: The implants were well tolerated, with minimal-to-mild clinical and microscopic ocular findings attributable to either the placebo or drug-loaded devices. Mild conjunctival congestion persisted through week 13 of the study and tended to correlate with the number of devices and presence of drug. Ophthalmic examinations revealed no effects beyond conjunctival surface hyperemia. No effects on the IOP, corneal thickness, or ERG parameters were observed. The lack of changes in the IOP was expected due to the known lack of the IOP-lowering effects in rabbits from latanoprost. Microscopically, implants at the 3-month necropsy were associated with subconjunctival tissue cavities (containing the implants), fibrous encapsulation, and an infiltrate of lymphocytes and macrophages, sometimes as multinucleate cells, into the subconjunctival implant cavity. The drug-containing implants were often associated with inflammatory cell infiltrates, including heterophils (neutrophils), within the implant subconjunctival cavities and adjacent to the implant sites. At the 9-month necropsy, heterophils were no longer common among the inflammatory cell infiltrates; macrophages and lymphocytes persisted; most of the biodegradable implants were fragmented and disintegrating; and fibrovascular proliferation was present within implant luminal remnants. None of the findings were considered adverse. Systemic exposures were above the limit of quantification (0.1 ng/mL) for up to 96 h in the higher-dose groups, consistent with the initial burst phase of compound release. CONCLUSION: Overall, the study supports the safety of the latanoprost-containing subconjunctival device as a means of extended delivery of the antiglaucoma medication. Latanoprost-containing subconjunctival implants were well tolerated by Dutch-belted rabbits for up to 9 months. Such devices may improve patient compliance and serve as a means of extended delivery of antiglaucoma medications.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

PURPOSE: To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. METHODS: Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a ß-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. CONCLUSIONS: From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable.

Long-term medical management of primary open-angle glaucoma and ocular hypertension in the UK: optimizing cost-effectiveness and clinic resources by minimizing therapy switches.

PURPOSE: The objective was to assess the long-term economic consequences of the medical management of glaucoma in the UK. METHODS: The economic evaluation was conducted using the results from a 10-year Markov model based around 3 key triggers for a switch in medical therapy for glaucoma, namely: lack of tolerance (using hyperemia as a proxy); intraocular pressure (IOP) not meeting treatment benchmark; and glaucoma progression. Clinical data from a comprehensive systematic literature review and meta-analysis were used. Direct costs associated with glaucoma treatment are considered (at 2008/9 prices) from the perspective of the UK NHS as payer (outpatient/secondary care setting). Using this model, the economic consequences of 3 prostaglandin-based treatment sequences were compared. RESULTS: Drug acquisition costs account for around 8% to 13% of the total cost of glaucoma and, if ophthalmologist visits are included, amount to approximately £0.80 to £0.90 per day of medical therapy. The total long-term costs of all prostaglandin strategies are similar because of a shift in resources: increased drug costs are offset by fewer clinic visits to instigate treatment switches, and by avoiding surgery or costs associated with managing low vision. Under the latanoprost-based strategy, patients would have longer intervals between the need to switch therapies, which is largely due to a reduction in hyperemia, seen as a proxy for tolerance. This leads to a delay in glaucoma progression of 12 to 13 months. For every 1000 clinic appointments, 719 patients can be managed for 1 year with a latanoprost-based strategy compared with 586 or 568 with a bimatoprost or travoprost-based strategy. CONCLUSIONS: Drug acquisition costs are not a key driver of the total cost of glaucoma management and the cost of medical therapy is offset by avoiding the cost of managing low vision. Economic models of glaucoma should include the long-term consequences of treatment as these will affect cost-effectiveness. This analysis supports the hypothesis that the economic and clinical benefits can be optimized by minimizing therapy switches.

Latanoprost versus timolol as first choice therapy in patients with ocular hypertension. A cost-effectiveness analysis.

PURPOSE: To determine the cost-effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol. METHODS: Two strategies for OH therapy are modelled, (1) 'starting with timolol' and (2) 'starting with latanoprost'. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side-effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow-up with IOP-dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP-lowering effect of drugs is based on meta-analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients. RESULTS: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (±0.017) mm Hg (strategy 1) and to 16.5 (±0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were € 367 and € 469, respectively. Lifetime blindness and costs were 0.0334 years and € 3,514 (strategy 1) and 0.0318 years and € 4,397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately € 537,000. CONCLUSION: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high.

Evaluation of investigator bias in industry-funded clinical trials of latanoprost.

OBJECTIVE: To determine whether sponsorship of prostaglandin analogue (PGA) clinical trials results in investigator bias in outcomes when studying intraocular pressure (IOP). DESIGN: Retrospective, observational cohort study. METHODS: A PubMed search was performed for latanoprost or Xalatan, bimatoprost or Lumigan, and travoprost or Travatan, with limits to humans, clinical trials, and English language. Inclusion criteria included randomized controlled trials, open-angle glaucoma, monotherapy with a PGA, baseline IOP ≥ 21 mm Hg, washout period, and minimum 1-month follow-up. Each article was reviewed by 2 independent reviewers. The results of IOP for each PGA were categorized as being sponsored by the parent company (the company manufacturing the PGA); by the competing company (the company manufacturing competing glaucoma therapy); or by a nonindustry source. The mean IOP and changes in IOP from baseline were compared among the 3 categories of sponsorship. RESULTS: Only studies involving latanoprost were analyzed because of the low number of studies meeting the inclusion criteria for bimatoprost and travoprost. We found 29 and 13 studies that provided 1- and 3-month data, respectively, for analysis. The mean baseline IOPs in the 3 groups (parent company, competing company, nonindustry) were not significantly different (p = 0.47). The mean IOP at 1 (p = 0.72) and 3 months (p = 0.59) and the change in IOP from baseline (p = 0.83 and 0.90, respectively) were not significantly different in the 3 groups. A random-effects metaregression controlling for the covariates of blinding, naïveté to PGAs, and baseline IOP < 24 mm Hg or ≥ 24 mm Hg did not change the findings. CONCLUSION: There was no evidence of investigator bias in determining outcomes for IOP in these clinical trials of latanoprost.