Anti-VEGF treatment of macular edema associated with retinal vein occlusion: patterns of use and effectiveness in clinical practice (ECHO study report 2).

PURPOSE: To evaluate the efficacy, safety, and injection frequency of vascular endothelial growth factor (VEGF) antagonists in the treatment of macular edema secondary to retinal vein occlusion (RVO) in clinical practice. PATIENTS AND METHODS: A multicenter retrospective study of the medical records of 165 patients (95 branch RVO, 70 central RVO) treated with at least three anti-VEGF injections in the study eye was conducted. Available data collected for at least 6 months after the first injection included Snellen best-corrected visual acuity (BCVA), central retinal thickness (CRT) by time-domain optical coherence tomography (TD-OCT) or spectral-domain optical coherence tomography (SD-OCT), anti-VEGF injections, other treatments/procedures for RVO, and adverse events. RESULTS: At baseline prior to anti-VEGF treatment, mean BCVA was 20/80 Snellen equivalent and mean CRT was 499 µm. Mean number of anti-VEGF injections received was 7.1 during the first year, 5.4 during the second year, and 5.9 during the third year; 51.3% (842/1,641) of injections were ranibizumab, 44.1% (724/1,641) were bevacizumab, and 4.6% (75/1,641) were aflibercept. One in five patients received concomitant focal laser treatment. The percentage of patients achieving both BCVA of 20/40 or better and CRT ≤250 µm on TD-OCT or ≤300 µm on SD-OCT at the same visit (primary endpoint) was 26.1% (30/115) after the first anti-VEGF injection and ranged from 20.0% (7/35) to 36.7% (11/30) after the first 16 injections. After each anti-VEGF injection from the 1st to the 16th, <60% of patients achieved 20/40 or better BCVA and ≤70% of patients achieved CRT ≤250 µm on TD-OCT or ≤300 µm on SD-OCT. The most common treatment-related adverse event was blurry or cloudy vision. CONCLUSION: In this real-world study, a mean of five to seven anti-VEGF injections was administered yearly, and the response to anti-VEGF therapy was suboptimal in many patients. Anti-VEGF therapy was well tolerated.

Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1).

PURPOSE: To evaluate the efficacy, safety, and injection frequency of vascular endothelial growth factor (VEGF) inhibitors as used in clinical practice for the treatment of diabetic macular edema. METHODS: Multicenter (10 sites), retrospective chart review in patients (n=156) who received ≥3 anti-VEGF injections. Data collected for ≥6 months after the first injection included Snellen best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by time-domain or spectral-domain optical coherence tomography (TD-OCT or SD-OCT). RESULTS: Mean number of anti-VEGF injections (627 bevacizumab, 594 ranibizumab, 1 aflibercept) was 5.8 (year 1), 5.0 (year 2), and 3.4 (year 3). Percentage of patients with BCVA of 20/40 or better and CRT ≤250 µm on TD-OCT or ≤300 µm on SD-OCT at the same visit (primary endpoint) ranged from 16.4% to 38.9% after the first 10 injections; 51.9%-62.3% achieved ≥20/40 BCVA and 26.2%-48.0% met CRT criteria. Therapy was well tolerated with 19 treatment-related adverse events (all ocular) reported. CONCLUSION: Anti-VEGF injections were administered less frequently and were less effective than those in the ranibizumab registration trials. After each of the first 9 injections, <25% of patients achieved both BCVA of 20/40 or better and a dry macula. A substantial proportion of patients are suboptimal responders to anti-VEGF therapy; these patients may be candidates for other therapies, including intravitreal corticosteroid and laser therapy.

Development and Validation of the Eyelash Satisfaction Questionnaire.

BACKGROUND: Patient-reported outcome (PRO) measures have been used to assess treatment benefit in a variety of therapeutic areas and are now becoming increasingly important in aesthetic research. OBJECTIVES: The objective of the current study was to develop and validate a new PRO measure (Eyelash Satisfaction Questionnaire [ESQ]) to assess satisfaction with eyelash prominence. METHODS: The content of the questionnaire (including conceptual framework and questionnaire items) was generated by review of literature, participant interviews, and expert opinion. Cognitive interviews were conducted to pilot test the questionnaire. Psychometric properties of the questionnaire were examined in a combined sample of participants (n = 970) completing Internet- (n = 909) and paper-based (n = 61) versions. Item- and domain-level properties were examined using modern and classical psychometrics. RESULTS: Content-based analysis of qualitative data demonstrated the presence of 3 distinct domains (Length, Fullness, Overall Satisfaction; Confidence, Attractiveness, and Professionalism; and Daily Routine). Initial confirmatory factor analysis (CFA) results of 23 items revealed insufficient model-data fit (comparative fit index [CFI] of 0.86 and a non-normed fit index [NNFI] of 0.82). A revised model using 9 items (3 per domain) achieved appropriate fit (CFI of 0.99 and NNFI of 0.97). Analyses revealed measurement equivalence across the Internet- and paper-based versions. The 3 ESQ domains had strong internal consistency reliability (Cronbach's α [range] = 0.919-0.976) and adequate convergent and discriminant validity. CONCLUSIONS: The ESQ was found to be a reliable and valid PRO measure for assessing satisfaction with eyelash prominence. LEVEL OF EVIDENCE 3: Therapeutic.

Two or more dexamethasone intravitreal implants in treatment-naïve patients with macular edema due to retinal vein occlusion: subgroup analysis of a retrospective chart review study.

BACKGROUND: Dexamethasone intravitreal implant (DEX implant) is a biodegradable, sustained-release implant that releases dexamethasone for up to 6 months. We evaluated the efficacy and safety of DEX implant in the treatment of macular edema secondary to retinal vein occlusion (RVO) in treatment-naïve patients. METHODS: A multicenter, retrospective, open-label chart review study investigated the efficacy and safety of DEX implant treatment in 289 patients with macular edema secondary to branch or central RVO (BRVO, CRVO) who received ≥2 treatments with DEX implant in the study eye. Concomitant adjunctive RVO treatments were permitted. Data collected from the time of the first implant (baseline) to 3-6 months after the last implant included best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography. In this subgroup analysis, we evaluated outcomes in patients who had received no previous treatment for RVO complications. RESULTS: Thirty-nine patients were treatment-naïve at the time of their first DEX implant (18 BRVO, 21 CRVO). Before the initial DEX implant, the mean duration of macular edema in treatment-naïve patients was 4.9 months, mean central retinal thickness was 550 µm, and mean Early Treatment Diabetic Retinopathy Study BCVA was 8.5 lines (20/125 Snellen). Treatment-naïve patients received a mean of 2.9 implants, either as monotherapy (n = 12) or with adjunctive RVO treatments (n = 27). The mean interval between implants was 177 days. After the first through sixth implants, mean changes from baseline BCVA ranged from +3.0 - +8.0 lines, and mean decreases from baseline central retinal thickness ranged from 241-459 µm. BCVA improved in both BRVO and CRVO and in both phakic and pseudophakic eyes. Overall, 83.8 % of treatment-naïve patients gained ≥2 lines in BCVA, 70.3 % gained ≥3 lines in BCVA, and 56.4 % achieved central retinal thickness ≤250 µm. The most common adverse event was increased intraocular pressure. Fifteen treatment-naïve patients had intraocular pressure ≥25 mm Hg; none required laser or incisional glaucoma surgery. CONCLUSION: Treatment with 2 or more DEX implants had a favorable safety profile and improved visual acuity and anatomic outcomes when used, either alone or with adjunctive RVO therapy, as initial treatment for RVO-associated macular edema. TRIAL REGISTRATION: ClinicalTrials.gov NCT01411696 , registered on August 5, 2011.

Two or more dexamethasone intravitreal implants as monotherapy or in combination therapy for macular edema in retinal vein occlusion: subgroup analysis of a retrospective chart review study.

BACKGROUND: Dexamethasone intravitreal implant (DEX implant) is a sustained-release biodegradable implant approved for treatment of macular edema associated with retinal vein occlusion (RVO). The safety and efficacy of treatment of RVO-associated macular edema with sequential DEX implants in clinical practice was evaluated in patients who received DEX implant as monotherapy compared with patients who received DEX implant in combination with other RVO treatments. METHODS: A multicenter, retrospective, open-label chart review study (one study eye/patient) evaluated use of DEX implant and outcomes in 289 patients with branch or central RVO who received at least 2 DEX implant treatments in the study eye. Data were collected from the time of the first implant (baseline) to 3-6 months after the last implant. Subgroup analysis evaluated outcomes in patients receiving only DEX implant during the study versus patients receiving DEX implant plus adjunctive RVO treatments. Endpoints included best-corrected visual acuity (BCVA) and central retinal thickness (CRT) change from baseline. RESULTS: DEX implant was used as monotherapy in 84 (29.1%) patients and in combination with other therapy in 205 (70.9%) patients. Mean number of DEX implant treatments received was 3.1 in the monotherapy group and 3.3 in the combination therapy group (P = 0.344). Mean time between implants was longer in the combination therapy group (177 vs. 151 days, P < 0.001). Mean change from baseline BCVA after the first through sixth DEX implants ranged from +0.6 to +3.4 lines in the monotherapy group and +1.3 to +2.8 lines in the combination therapy group. Mean decrease from baseline CRT ranged from 165 to 230 µm in the monotherapy group and 136 to 175 µm in the combination therapy group. Increased intraocular pressure was more common in the combination therapy group. CONCLUSIONS: Treatment of RVO-associated macular edema with at least 2 sequential DEX implants was safe and effective both when used alone and when combined with other RVO treatments. Improvements in BCVA and CRT were generally similar in the monotherapy and combined therapy groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT01411696 .

Development of a preference-based index from the National Eye Institute Visual Function Questionnaire-25.

IMPORTANCE: Understanding how individuals value health states is central to patient-centered care and to health policy decision making. Generic preference-based measures of health may not effectively capture the impact of ocular diseases. Recently, 6 items from the National Eye Institute Visual Function Questionnaire-25 were used to develop the Visual Function Questionnaire-Utility Index health state classification, which defines visual function health states. OBJECTIVE: To describe elicitation of preferences for health states generated from the Visual Function Questionnaire-Utility Index health state classification and development of an algorithm to estimate health preference scores for any health state. DESIGN, SETTING, AND PARTICIPANTS: Nonintervention, cross-sectional study of the general community in 4 countries (Australia, Canada, United Kingdom, and United States). A total of 607 adult participants were recruited from local newspaper advertisements. In the United Kingdom, an existing database of participants from previous studies was used for recruitment. INTERVENTIONS: Eight of 15,625 possible health states from the Visual Function Questionnaire-Utility Index were valued using time trade-off technique. MAIN OUTCOMES AND MEASURES: A θ severity score was calculated for Visual Function Questionnaire-Utility Index-defined health states using item response theory analysis. Regression models were then used to develop an algorithm to assign health state preference values for all potential health states defined by the Visual Function Questionnaire-Utility Index. RESULTS: Health state preference values for the 8 states ranged from a mean (SD) of 0.343 (0.395) to 0.956 (0.124). As expected, preference values declined with worsening visual function. Results indicate that the Visual Function Questionnaire-Utility Index describes states that participants view as spanning most of the continuum from full health to dead. CONCLUSIONS AND RELEVANCE: Visual Function Questionnaire-Utility Index health state classification produces health preference scores that can be estimated in vision-related studies that include the National Eye Institute Visual Function Questionnaire-25. These preference scores may be of value for estimating utilities in economic and health policy analyses.

Topical cyclosporine versus emulsion vehicle for the treatment of brittle nails: a randomized controlled pilot study.

BACKGROUND: Limited options are available for the treatment of brittle nail syndrome. OBJECTIVE: To assess the efficacy and safety of topical cyclosporine emulsion (CsAE) versus emulsion (vehicle) alone in the treatment of brittle nail syndrome. RESULTS: Twenty-four patients were randomized to topical CsAE emulsion or emulsion (vehicle) for 24 weeks. Four fingernails of each patient were included; the 2 most severe brittle nails and the second most normal nail were treated with the same medication. The fourth nail, the most normal nail, remained untreated and was used to assess nail growth. The prespecified primary endpoint was change from baseline in Physician Global Assessment (PGA) score (0 to 5 scale) at each follow-up visit. Safety evaluations were conducted at each visit. RESULTS: In the intent-to-treat population (n=12 for each treatment arm), the PGA score for treated nails improved from baseline (CsAE, 0.7 to 1.4; emulsion, 0.7 to 1.5; P<0.05 for each), with no significant between-group differences. Untreated nails did not improve in overall appearance (0.0 to 0.3 grade; P>0.05). Statistically and clinically significant improvement from baseline was reported for nail length/appearance in both CsAE and vehicle groups. LIMITATIONS: Sample size was relatively small. The difference in PGA between treated and untreated nails was not analyzed. Baseline disease severity may have been too mild, limiting detection of efficacy. CONCLUSIONS: Both CsAE and emulsion vehicle applied topically appeared to improve signs and symptoms of brittle nail syndrome and were well tolerated. These findings warrant corroboration in a larger population and inclusion of comparison with an inactive control and a higher concentration of CsAE, the former which may help in distinguishing the efficacy of vehicle emulsion from CsAE.

Efficacy and safety of two or more dexamethasone intravitreal implant injections for treatment of macular edema related to retinal vein occlusion (Shasta study).

PURPOSE: To evaluate the efficacy, safety, and reinjection interval of dexamethasone intravitreal implant (DEX implant) in branch retinal vein occlusion and central retinal vein occlusion patients receiving ≥ 2 DEX implant treatments. METHODS: Multicenter (26-site), retrospective chart review study. Data were collected from baseline (at first DEX implant) through 3 months to 6 months after last DEX implant. RESULTS: Patients (n = 289) received 2 to 9 (mean, 3.2) DEX implants as monotherapy (29.1% of patients) or with adjunctive treatments/procedures. Mean duration of macular edema before first DEX implant was 18.4 months. Mean reinjection interval was 5.6 months. Mean peak change in best-corrected visual acuity from baseline through 4 weeks to 20 weeks after final DEX implant was +1.0 line (P < 0.001). Best-corrected visual acuity and central retinal thickness improved significantly from baseline after each of the first 6 DEX implant injections (P ≤ 0.037); 59.7% of branch retinal vein occlusion and 66.7% of central retinal vein occlusion patients achieved ≥ 2-line best-corrected visual acuity improvement. Intraocular pressure increase (≥ 10 mmHg) occurred in 32.6% of patients; 29.1% used intraocular pressure-lowering medication to treat increases associated with DEX implant. Only 1.7% of patients required incisional glaucoma surgery. CONCLUSION: Retinal vein occlusion patients treated with multiple DEX implant injections, either alone or combined with other therapies, had improved central retinal thickness and visual acuity with each subsequent injection. No new safety concerns developed with multiple implants.

Patient-reported outcomes of bimatoprost for eyelash growth: results from a randomized, double-masked, vehicle-controlled, parallel-group study.

BACKGROUND: Hypotrichosis of the eyelashes may negatively influence an individual's self-perception and appearance. Assessing the impact of treatment from a patient's perspective may be particularly relevant in trials of aesthetic agents. Once-daily dermal (topically applied) administration of bimatoprost ophthalmic solution 0.03% has been associated with increased eyelash prominence (ie, length, thickness, darkness). OBJECTIVES: The authors assess patient-reported outcomes (PRO) after treatment with bimatoprost for hypotrichosis of the eyelashes. METHODS: In this multicenter, double-masked, randomized, vehicle-controlled, parallel clinical trial, 4 PRO questionnaires were distributed to 278 patients (bimatoprost [n = 137] and vehicle [n = 141]). The primary PRO questionnaire was the 23-item Eyelash Satisfaction Questionnaire (ESQ), which measured satisfaction in 3 domains: length, fullness, and overall satisfaction (LFOS); confidence, attractiveness, and professionalism (CAP); and impact on daily routine (DR). RESULTS: By week 16, the bimatoprost group reported significantly greater improvements from baseline on all ESQ items (P ≤ .0433). These improvements were sustained through the 4-week posttreatment study visit. Patient satisfaction was significantly greater in the bimatoprost group than in the vehicle group for all 3 domains: LFOS (weeks 8-20; P ≤ .0052), CAP (weeks 12-20; P < .0001), and DR (weeks 16 and 20; P ≤ .01). CONCLUSIONS: The bimatoprost group reported significantly greater levels of positive patient outcomes and satisfaction than the vehicle group across all 23 questions and all 3 domains of the primary PRO questionnaire. These results support the effectiveness, as measured by objective measures and PRO, of once-daily bimatoprost ophthalmic solution 0.03% at producing more prominent eyelashes in adults.

Rasch analysis in the development of a simplified version of the National Eye Institute Visual-Function Questionnaire-25 for utility estimation.

PURPOSE: Preference-based health measures value how people feel about the desirability of a health state. Generic measures may not effectively capture the impact of vision loss from ocular diseases. Disease-targeted measures could address this limitation. This study developed a vision-targeted health state classification system based on the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). METHODS: Secondary analysis of NEI VFQ-25 data from studies of patients with central (n = 932)- and peripheral-vision loss (n = 2,451) were used to develop a health state classification system. Classical test theory and Rasch analyses were used to identify a smaller set of NEI VFQ-25 items suitable for the central- and peripheral-vision-loss groups. RESULTS: Rasch analysis of the NEI VFQ-25 items using the peripheral vision-loss data indicated that 11 items fit a unidimensional model, while 14 NEI VFQ-25 items fit using the central-vision-loss data. Combining peripheral-vision-loss data and central-vision-loss data resulted in 9 items fitting a unidimensional model. Six items covering near vision, distance vision, social vision, role difficulties, vision dependency, and vision-related mental health were selected for the health-state classification. CONCLUSIONS: The derived health-state classification system covers relevant domains of vision-related functioning and well-being.

Psychometric evaluation of the Glaucoma Symptom Identifier.

OBJECTIVE: To evaluate the psychometric properties of the Glaucoma Symptom Identifier (GSI), a tool designed to assess multiple possible glaucoma symptoms and their impact on quality of life in clinical practice. We sought to address the need for better methods to assess visual function related to quality of life of glaucoma patients with a tool to show to both physicians and their patients that glaucoma is not an asymptomatic disease. The development process was to provide comprehensive assessment in 1 page of the impact of glaucoma on patients' quality of life by including an exhaustive list of unique and nonredundant items. DESIGN: Cross-sectional online survey. PARTICIPANTS: Seven hundred and eighteen individuals with a self-reported diagnosis of glaucoma, who were at least 40 years of age. METHODS: The impact of glaucoma was assessed by asking study participants the degree of difficulty they experience on a number of tasks. Item response theory was used to psychometrically evaluate the GSI. Scores on the GSI and the SF-12, a generic quality-of-life instrument, were compared. MAIN OUTCOME MEASURES: Items in the GSI were categorized in terms of their ability to capture glaucoma impact on quality of life across the population range of subjects from mild-to-severe glaucoma severity. RESULTS: The GSI showed good reliability, and convergent and discriminant validity. Items in the GSI captured glaucoma impact on quality of life over an adequate range of disease severity. Potential improvements to the existing questionnaire were identified using item response theory modeling results and respondents' feedback on the survey. CONCLUSIONS: Our findings suggest that the GSI is a psychometrically valid tool, adequate for glaucoma patients' self-administration within a clinician's routine practice to help both the patient and physician assess the patient's current and potential future symptoms of glaucoma.

Paired-eye comparison of medical therapies for glaucoma.

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

Safety, effectiveness, and subjective experience with topical bimatoprost 0.03% for eyelash growth.

BACKGROUND: Ocularly applied bimatoprost 0.03% is associated with increased eyelash growth. OBJECTIVE: To assess the safety, efficacy, and subjective experience of using dermal application of bimatoprost 0.03% for the growth of natural eyelashes. METHODS: Prospective, open-label study of subjects who desired longer, thicker (fuller), and darker natural eyelashes. Bimatoprost was applied to the upper lid margin once daily for 12 weeks. Adverse events and intraocular pressure were assessed, and subjects completed health outcomes questionnaires. Eyelash growth and darkening were scored using photographs taken at weeks 1 and 12. RESULTS: All subjects were female (N=28). No serious or unexpected adverse events were reported. The mean change from baseline intraocular pressure was less than 1 mmHg at each time point, but was statistically significant at weeks 1 and 4 (p< or =.047). At week 12, all subjects had noticed significant growth or darkening. Post hoc analysis of photographs corroborated these reports (p<.001). CONCLUSION: Bimatoprost was found safe for eyelid application and was associated with enhanced eyelash growth. All subjects noticed favorable changes in the appearance of their eyelashes.

Minimal clinically important difference for the ocular surface disease index.

OBJECTIVE: To assess the minimal clinically important difference (MCID) for the Ocular Surface Disease Index (OSDI; Allergan Inc, Irvine, California, holds the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease. METHODS: Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI). RESULTS: Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease. CONCLUSIONS: Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

Comparing adherence and persistence across 6 chronic medication classes.

BACKGROUND: The National Quality Forum recently endorsed the proportion of days covered (PDC)-a measure of medication adherence-as an indicator of quality in drug therapy management. OBJECTIVE: To inform initial efforts to improve the quality of drug therapy management, we compared PDC and persistence among new users of 6 commonly used chronic medication categories. METHODS: A retrospective analysis of pharmacy claims in a database of more than 64 million members enrolled in 100 health plans assessed persistence and adherence to drug therapy in 6 chronic conditions. Patients were included in the analysis if they initiated a prescription drug of interest in any of 6 drug classes-prostaglandin analogs, statins, bisphosphonates, oral antidiabetics, angiotensin II receptor blockers (ARBs), and overactive bladder (OAB) medications-between January 1 and December 31, 2005. The first claim for a drug of interest during this period was considered a patient's index date. Patients were required to have a minimum of 12 months of continuous enrollment both preceding and following their index date. New users of a treatment were identified by excluding patients who filled a prescription for any drug in the same class during the previous 12 months and were followed for a minimum of 12 months. Nonpersistence was defined as discontinuation of the therapy class following an allowed gap between refills-30-, 60-, and 90-day refill gaps were used. Adherence was defined as a continuous measure of the proportion of days covered (PDC) during the 12-month post-index period. Logistic regression analyses predicted (a) nonpersistence during the 12-month post-index period and (b) adherence (PDC) of at least 80%, with drug class as the predictor variable of interest, controlling for demographic variables, insurance and plan type, history of hospitalization, Charlson comorbidity score, copayment for index medication, and number of medications at index. RESULTS: A total of 167,907 patients were identified across 6 cohorts. Using the 60-day gap, 6-month persistence rates were prostaglandin analogs 47%, statins 56%, bisphosphonates 56%, oral antidiabetics 66%, ARBs 63%, and OAB medications 28%. After the first 90 days of therapy, relative persistence was stable across cohorts, and rates declined consistently from 6 months post-index to study end. Logistic regression models showed that oral antidiabetic users had a 59%, 36%, 37%, and 79% decreased risk of nonpersistence in a 12-month follow-up period compared with patients taking prostaglandin analogs, statins, bisphosphonates, or OAB medications, respectively. Risk of nonpersistence decreased with increasing age. Mean (SD) 12-month adherence rates were: prostaglandin analogs 37% (26%), statins 61% (33%), bisphosphonates 60% (34%), oral antidiabetics 72% (32%), ARBs 66% (32%), and OAB medications 35% (32%). Logistic regression indicated that oral antidiabetic use was a significant predictor of adherence (PDC) of at least 80% compared with other therapy classes. Adjusted odds ratios for oral antidiabetics were 17.60 (95% confidence interval [CI] = 15.38-20.14) versus prostaglandin analogs, 2.06 (95% CI = 1.99-2.12) versus statins, 1.92 (95% CI = 1.83-2.02) versus bisphosphonates, 1.29 (95% CI = 1.24-1.34) versus ARBs, and 5.77 (95% CI = 5.38-6.19) versus OAB medications. CONCLUSION: This analysis of adherence (PDC) and persistence across a sample of 6 chronic therapies found variable but uniformly suboptimal medication use. Adherence to prostaglandin eye drops and OAB medications was lower than to cardiovascular, oral antidiabetic, and oral osteoporosis therapies. These findings provide useful baseline information for the development of initiatives to improve the quality of drug therapy management.

Healthcare charges in patients who transition from ocular hypertension to primary open-angle glaucoma based on ophthalmic coding data.

INTRODUCTION: The purpose of this research was to assess the impact of transition from ocular hypertension (OHT) to primary open-angle glaucoma (POAG) on healthcare charges. METHODS: A case-control group was identified using PharMetrics claims database (1998-2005). Cases (n=1055) had a transition from OHT to POAG based on International Classification of Disease, Ninth Edition coding (ICD-9=365.11). Controls (n=2110) retained an ICD-9 code for OHT (ICD-9=365.04) and were matched to cases (2:1) on gender, age, diagnosis year, and follow-up time post-diagnosis. The index date marked the transition for cases and a date of similar duration after OHT diagnosis for controls. Conditional logistic regression and multiple linear regression models determined the impact of transitioning on healthcare charges. RESULTS: Cases had significantly higher increases in ophthalmology-related charges ($797 vs. -$385, P<0.0001) but similar total healthcare charges ($1689 vs. $1386, P=0.8277) from the year pre- to year post-index date when compared with controls. After adjusting for key covariates, cases were 1.56 times (95% CI: 1.33-1.82) more likely to have increased total charges and 5.26 times (95% CI: 4.27-6.47) more likely to have increased ophthalmology-related charges compared with controls. In multiple linear regression analyses, cases experienced $48 (55%) higher increases in ophthalmology-related charges from the year pre- to year post-index date compared with controls ($85 vs. $37, respectively; P<0.0001). CONCLUSION: Patients with a transition from OHT to POAG based on ICD-9 coding had higher ophthalmology-related charges the year after transition compared with patients who retained a code for OHT. Prevention of this transition could result in healthcare resource savings.

Glaucoma medication persistence with a fixed combination versus multiple bottles.

OBJECTIVE: To determine if prescribing combination therapy versus two or three separate bottles results in greater persistence among patients with glaucoma. METHODS: Using a retail pharmacy claims database, three glaucoma patient cohorts were defined and followed for 12 months (January 2004 through December 2004). Patients in cohort 1 had a prescription for a single fixed-combination therapy during the month of January 2004. Cohort 2 consisted of patients with prescriptions for a beta-blocker and one other glaucoma product in the same month. Cohort 3 comprised patients with prescriptions filled for three different glaucoma therapies during the first month. A fixed-combination formulation may have been included in cohorts 2 and 3 as well, but was counted as a single bottle. Persistence rate, defined as the percentage of patients who did not discontinue their medication over the 12-month period, was calculated. RESULTS: Cohort 1 (one bottle; n = 14 742) was more persistent than cohort 2 (two bottles; n = 18 411), with 35.3% vs. 27.2% of patients remaining on therapy at the end of the study period (p < 0.0001). Cohort 3 (n = 4826), with three separate bottles per patient, had the lowest percentage remaining on therapy (23.9%; p < 0.0001). CONCLUSION: Analyses of pharmacy database data are limited by the possibilities of misidentifying newly treated patients or misclassifying added versus switched medications. As the number of separate products used for glaucoma therapy increases, patient persistence decreases. A management regimen requiring as few products as possible may enhance glaucoma patient persistence.

The relationship of mean deviation scores and resource utilization among patients with glaucoma: a retrospective United States and European chart review analysis.

PURPOSE: To determine the relationship between mean deviation (MD) scores and resource utilization among glaucoma patients in the United States and Europe. METHODS: A retrospective analysis of patient in the United States (June 1990 to January 2003, N=151) and Europe (June 1994 to July 2003, N=194) was conducted. Office visits, pressure-lowering medications, visual field examinations, and glaucoma surgeries were recorded with age, intraocular pressure (IOP), and MD. Patients with missing MD and IOP were excluded; final sample sizes were 130 in the United States and 161 in Europe. Fixed effects and logistic regression models assessed the associations between MD and visits, medication, examinations, and surgery. RESULTS: Number of office visits and visual field examinations significantly increased but the number of glaucoma medications decreased as MD worsened and IOP increased. Odds of trabeculoplasty within 2 years decreased by 8.1% in the United States and 9.9% in Europe with every 1.0 dB improvement in MD. Odds of trabeculectomy within 2 years increased by 13.9% in the United States and by 18.6% in Europe with every 1 mm Hg increase in IOP. In the United States, odds of trabeculectomy within 5 years increased by 12.2% with each 1.0 dB worsening in MD. CONCLUSIONS: MD is associated with resource utilization in glaucoma patients. Evidence supporting use of MD to predict surgery is less conclusive, possibly due to the relative low frequency of surgeries. Therapies aimed at stabilizing visual field deterioration may reduce resource use and costs associated with glaucoma; however, more research is necessary to establish whether such treatments meet common standards of cost-effectiveness.

Pharmacotherapy compliance in patients with ocular hypertension or primary open-angle glaucoma.

PURPOSE: The aim of this study was to compare rates of pharmacotherapy coverage in patients with ocular hypertension (OH) and patients with primary open-angle glaucoma (POAG). METHODS: Retrospective cohort study analysis of a nationally representative, multimanaged health plan database (PharMetrics; 1998-2005) which included 4818 medicated OH patients and 52,985 medicated POAG patients with at least 1 year of continuous enrollment and at least one prescription for IOP-lowering medication during the first year of follow-up. Patients selected for the current study were nested within the cohort of OH patients (n = 36,767) and POAG patients (n =72,412) previously reported. Of the previously reported OH cohort, only 13.1% of patients filled at least one prescription, as compared to 73.2% of the previously reported POAG cohort. Medication coverage was defined as the percent of days during which a patient was in possession of IOP-lowering therapy over the first year of follow-up (medication coverage = number of covered days/365). Compliant patients were defined as those with >or= 75th percentile medication coverage. RESULTS: POAG patients had slightly longer mean length of enrollment in the database (2.5 years, SD = 1.2) than did OH patients (2.4 years, SD = 1.1; P < 0.0001). The mean medication coverage was 50% for the POAG cohort (SD = 0.26) and 40% for the OH cohort (SD = 0.25; P < 0.0001). In multivariate models controlling for key covariates of interest, POAG patients were 1.9 (95% CI: 1.7 to 2.0) times more likely to be compliant with their pharmacotherapy than OH patients. CONCLUSION: In general, pharmacotherapy coverage was poor. Patients with POAG, a more severe condition, were significantly more covered with pharmacotherapies than patients with OH. It is important to implement strategies to help improve patient coverage prior to occurrence of more severe disease.

Assessing quality of life in patients with glaucoma using the Glaucoma Quality of Life-15 (GQL-15) questionnaire.

PURPOSE: To measure and compare quality of life in patients with and without glaucoma using the Glaucoma Quality of Life-15 Questionnaire, and to determine the association between glaucoma-related quality of life and clinical indices of glaucoma. PATIENTS AND METHODS: Using a prospective, cross-sectional study, we collected demographic information via interviews and administered the questionnaire to assess glaucoma-related quality of life in 121 patients with glaucoma and 31 subjects without glaucoma. Visual function was measured objectively by clinical examination. Group differences and the association between questionnaire scores and clinical indices were evaluated using nonparametric analysis of variance and correlation coefficients, respectively. The relationship between the likelihood of reporting vision-related dysfunction and glaucoma severity was examined using logistic regression. RESULTS: Patients with glaucoma had significantly poorer glaucoma-related quality of life than controls (P<0.001). Summary scores differed significantly among patients with mild, moderate, and severe glaucoma demonstrating a trend of poorer quality of life with increasing disease severity. Activities involving glare and dark adaptation were most problematic for all, but patients with glaucoma felt significantly more compromised in central and near vision, peripheral vision, and outdoor mobility (all P<0.001). Glaucoma-related quality of life scores correlated moderately and significantly with visual acuity, disease severity, and visual field measurements, but only severe glaucoma was a significant predictor of self-perceived deficits in glaucoma-related quality of life (P=0.038). CONCLUSIONS: The Glaucoma Quality of Life-15 Questionnaire correlated well with objective measures of visual function and discriminated between quality of life in patients with glaucoma and subjects without glaucoma.