The impact of ocular adverse effects in patients treated with topical prostaglandin analogs: changes in prescription patterns and patient persistence.

PURPOSE: To document patient/physician perceptions of adverse effects and their relationship to medication changes among patients prescribed prostaglandin analogs. METHODS: Medical/pharmacy claims (private U.S. health network) identified patients filling initial topical ocular hypotensive prescriptions from 2001 to 2004; 300 open-angle glaucoma patients prescribed a prostaglandin analog and 103 ophthalmologists were selected by algorithm for telephone interviews. Medical charts for 225/300 interviewed and 75 non-interviewed patients were abstracted. Medication patterns were assessed in pharmacy claims data. Frequency of adverse effects noted by physicians and associations with medication change decisions were examined in charted data. Patients' experiences with adverse effects were compiled from surveys. RESULTS: In patients treated with latanoprost (N = 4,071), bimatoprost (N = 1,199), or travoprost (N = 1,001), continuous refill of medication through 1 year was seen in 11%, 9%, and 5% of patients, respectively (P = 0.0001; retrospective pharmacy claims). Adverse effects were the second most common reasons noted by physicians for switching medications after lack of efficacy (19% vs. 43%, respectively). Adverse effects were noted in 65% of patient charts. Hyperemia was the most common adverse effect occurring with at least one other adverse effect in 48% of patients with the condition. CONCLUSIONS: Ocular adverse effects, particularly hyperemia, negatively affect patient continuation with therapy and switching.

Physician beliefs and behaviors related to glaucoma treatment adherence: the Glaucoma Adherence and Persistency Study.

PURPOSE: Patient adherence with topical glaucoma therapy is recognized as suboptimal. Though some studies have associated physician/patient interaction with adherence, little systematic research has explored the ophthalmologist's perspective of this interaction. Telephone interviews with physicians treating glaucoma were conducted to ascertain the extent to which multivariate analysis of physician demographics, beliefs, and behaviors could reveal differences potentially relevant to future adherence with topical glaucoma therapy for primary open-angle glaucoma, in conjunction with other phases of the Glaucoma Adherence and Persistency Study (GAPS). METHODS: Structured interviews were conducted with 103 ophthalmologists treating significant numbers of primary open-angle glaucoma patients in a national managed care network. To the maximum extent possible, eligible patients of physicians interviewed were included in the other GAPS phases (claims analysis, patient surveys, and medical chart reviews). RESULTS: Physicians reported a wide range of beliefs and behaviors regarding patients' medication adherence, but beliefs and behaviors were linked. The segmentation analysis yielded 3 clusters of physicians, which we have described on the basis of their predominant beliefs as "reactives," "skeptics," and "idealists." The "idealists," though the smallest group, more often reported beliefs and behaviors that may be more positively associated with patient adherence, especially in the context of other GAPS findings. CONCLUSIONS: Physician vigilance for opportunities to detect and address nonadherence is suggested, as is interventional research on the basis of the constructs identified.

Doctor-patient communication, health-related beliefs, and adherence in glaucoma results from the Glaucoma Adherence and Persistency Study.

OBJECTIVE: To use multiple data sources to determine drivers of patient adherence to topical ocular hypotensive therapy. DESIGN: Retrospective database and chart reviews in combination with prospective patient surveys. Diverse medical environments where insured patients in the research database seek care. PARTICIPANTS: Three hundred patients with a new claim diagnosis for open-angle glaucoma who initially were prescribed one of three prostaglandins and 103 physicians participating in the same medical plans. METHODS: A structured interview addressing self-reported adherence, experiences with medication, communication with the physician, and health-related beliefs associated with adherence behavior was administered to surveyed patients. Phone interviews were conducted with participating ophthalmologists. MAIN OUTCOME MEASURE: Of adherence, medication possession ratio. RESULTS: Eight variables were associated independently with a lower medication possession ratio: (1) hearing all of what you know about glaucoma from your doctor (compared with some or nothing); (2) not believing that reduced vision is a risk of not taking medication as recommended; (3) having a problem paying for medications; (4) difficulty while traveling or away from home; (5) not acknowledging stinging and burning; (6) being nonwhite; (7) receiving samples; and (8) not receiving a phone call visit reminder. The multivariate model explained 21% of the variance. CONCLUSIONS: These findings indicate that doctor-patient communications and health-related beliefs of patients contribute to patient adherence. Patient learning styles that are associated with less concern about the future effects of glaucoma and the risks of not taking medications are associated with lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive doctor-dependent patients who tend to be poorly adherent. These findings suggest that educational efforts in the office may improve patient adherence to medical therapies.

Switching from latanoprost to fixed-combination latanoprost-timolol: a 21-day, randomized, double-masked, active-control study in patients with glaucoma and ocular hypertension.

BACKGROUND: Approximately 40% of patients with glaucoma are concomitantly prescribed >or=2 different intraocular pressure (IOP)-lowering medications. An effective and well-tolerated fixed combination of agents requiring once-daily instillation may improve patient compliance. OBJECTIVE: The purpose of this study was to compare the efficacy and safety profile of the fixed combination latanoprost 0.005% + timolol maleate 0.5% QD with those of latanoprost 0.005% monotherapy QD in patients whose elevated IOP (>or=21 mm Hg) was inadequately controlled by latanoprost. METHODS: This 21-day, randomized, double-masked, active-control study was conducted at 49 study sites in Argentina, Brazil, Colombia, Mexico, Peru, the United States, and Venezuela. Adults with glaucoma or ocular hypertension who had failed to reach an IOP of <21 mm Hg while receiving latanoprost for at least 28 days were enrolled. After an additional 28 days of latanoprost run-in, patients were randomly assigned to continue latanoprost monotherapy or to switch to the fixed combination for 21 days. The intent-to-treat (ITT) population included all patients who received at least 1 dose of double-masked study medication; the per-protocol (PP) analysis included patients who completed the study without a major protocol violation and who had IOP measurements both at baseline and at day 21. The primary end point was the proportion of patients whose IOP was decreased >or=2 mm Hg from the baseline level on day 21. Proportions of patients demonstrating IOP decreases >or=3, >or=4, or >or=5 mm Hg from the baseline level and of patients reaching an 10P or=3, >or=4, or >or=5 mm Hg (for each target level, P < 0.001 vs latanoprost group) or final IOP 18 mm Hg (fixed -combination, 35.1%; latanoprost, 17.8%; P < 0.001). Both treatments were well tolerated. Similar proportions of patients in the fixed-combination and latanoprost groups reported at least 1 treatment-emergent AE (10.9% and 12.1%, respectively). CONCLUSION: In this selected population of patients with an inadequate initial IOP response to latanoprost, switching to fixed-combination latanoprosttimolol resulted in a greater decrease in IOP and similar tolerability compared with continuing latanoprost therapy.

Association between ocular herpes simplex virus and topical ocular hypotensive therapy.

PURPOSE: To evaluate whether use of particular topical hypotensive therapies is associated with ocular herpes simplex virus (OHSV). MATERIALS AND METHODS: This population-based, retrospective, cohort study used claims records from the Protocare Sciences managed care database (United States). Data were extracted from September 1, 1996 through June 30, 2002. An OHSV event was either a medical claim from the utilization database coded with an International Classification of Diseases Ninth Revision (ICD-9) code for OHSV (ICD-9 = 054.4, 054.40-054.44, 054.49) or a pharmacy claim for vidarabine or trifluridine ophthalmic solution. RESULTS: A total of 93,869 eligible glaucoma patients, 21 different ocular hypotensive agents, and 192,840 agent-utilizing patient combinations were identified. In all, 411 patients had an OHSV event; 272 of 411 patients had at least 1 ocular hypotensive agent dispensed prior to the OHSV event but not preceding the event by less than 7 days. Of these, 219 had only 1 ocular hypotensive agent dispensed on the last fill date prior to the OHSV event, yielding an overall OHSV event rate of 0.11%. There was no significant association between OHSV event rates and agent use for either the set of 21 agents (P = 0.260; chi2) or when 14 products having < 5% usage were combined (P = 0.058). Prevalence rates were estimated as 161 per 100,000 population for 2000 to 2001 and 165 per 100,000 for 1999 to 2001. CONCLUSIONS: Ocular herpes simplex virus is extremely rare in patients treated with ocular hypotensive therapies, and its prevalence is similar to that found in the general population. The current analysis revealed no association between the use of particular topical ocular hypotensive therapies and OHSV.

Gold standard medical therapy for glaucoma: defining the criteria identifying measures for an evidence-based analysis.

BACKGROUND: Over the past decade, several new medical therapies have become available for the treatment of primary open-angle glaucoma (POAG). A systematic evidence-based approach for identifying an optimal therapeutic agent is lacking. OBJECTIVES: The aims of this review were to critically evaluate published treatment recommendations for POAG and, based on a systematic review of the literature, to develop criteria that would define a "gold standard" medical therapy that reflects new treatment advances and established therapeutic goals. METHODS: A MEDLINE search spanning the years 1966 to 2002 and using the search terms gold standard, drug of choice, agent of choice, benchmark, ophthalmology, eye, and glaucoma was conducted and the results reviewed by a panel of 15 experts in the field of glaucoma. Published treatment recommendations for POAG were discussed. Criteria, anchored to medical evidence, for distinguishing a standard of medical therapy for POAG were defined. RESULTS: The terms connoting a gold standard therapy were found in only 258 of approximately 368,000 ophthalmology-related citations and 53 of almost 23,000 glaucoma citations, validating the need to define therapeutic standards. The lack of recommendations for the use of new classes of ocular hypotensive agents was acknowledged. Criteria identified to evaluate intraocular pressure (IOP)-lowering agents as gold standards included the following: efficacy in reducing IOP consistently over a 24-hour period to a level that will preserve the visual field and protect the optic nerve without inducing tachyphylaxis and tolerance, paucity of local and systemic adverse effects, promotion of patient compliance, and applicability in diverse patient populations. CONCLUSIONS: These criteria should be employed as measures for evidence-based analyses to evaluate available and future IOP-lowering medical therapies for POAG. The conceptual framework presented may be applicable to other therapeutic areas.

Intraocular pressure, safety, and quality of life in glaucoma patients switching to latanoprost from monotherapy treatments.

PURPOSE: To evaluate the efficacy, safety and quality of life in ocular hypertensive or open-angle glaucoma patients who required alteration in previous therapy and were changed to latanoprost. METHODS: A prospective, multicenter, active, historical controlled trial in which qualified patients had previous therapy substituted with latanoprost 0.005% and were followed for up to 6 months. RESULTS: 3179 patients were included in the intent-to-treat analysis. In all patients latanoprost reduced the intraocular pressure (IOP) from 20.1 +/- 3.9 to 17.1 +/- 3.5 mm Hg (p< 0.0001) and when compared to previous monotherapies: beta-blockers (-3.0 +/- 3.5, n = 1976), alpha-agonists (-3.6 +/- 3.7, n = 581), miotics (-2.8 +/- 3.0, n = 21), carbonic anhydrase inhibitors (-3.2 +/- 3.5, n = 198), and other prostaglandin analogs (-1.6 +/- 3.7, n = 402). The most common ocular adverse event with latanoprost was conjunctival hyperemia (n = 66, 2.0% incidence) and the most common systemic adverse event was headache (n = 9, 0.2%). Over the 6-month treatment interval 89.8% of patients were maintained on latanoprost. On the solicited symptom survey patients showed a preference for latanoprost compared to previous therapy for several reasons: (depending on the product) dryness, blurred vision, tearing, stinging on instillation, crusting, itching, fatigue, dizziness, despondency and dry mouth (p < 0.005). CONCLUSION: Latanoprost generally provides reduced IOP, limited side-effects, improvement in many quality of life measures and is maintained in patients who required a substitution from previous monotherapy.

Changing paradigms in the medical treatment of glaucoma.

Glaucoma is defined by a typical optic neuropathy accompanied by characteristic visual field loss and eventual blindness. The major risk factor for glaucoma is elevated intraocular pressure (IOP). Lowering IOP is currently the only proven method for reducing the risk of glaucomatous visual field loss and remains the primary goal of therapy. With the recent introduction of many new medications that lower IOP, the definition of what constitutes maximum tolerated medical therapy has been changing. The treatment can now be tailored better to each individual patient. The regimen needs to be affordable, easy to understand, and least interfering with the patient's quality of life. beta-blockers still are the mainstay of initial therapy, but more and more prostaglandin analogs and also alpha-2 agonists are being used initially. Systemic carbonic anhydrase inhibitors and cholinergics are being used less frequently.