Scott D. Lawrence

Sustained drug delivery in glaucoma.

Purpose of review This article reviews recently published studies and important clinical trials of novel drug delivery systems for glaucoma and evaluates the potential of these systems to provide sustained therapeutic benefits. Recent findings The efficacy of topical medications to lower intraocular pressure (IOP) is limited by poor patient adherence, low bioavailability of drug and the potential for local and systemic side effects. Recent studies highlight the potential for sustained drug delivery through innovative delivery platforms. Nanoparticle-based formulations, drug-eluting contact lenses, punctum inserts and bioadhesive matrices placed in the conjunctival sac can enhance drug delivery by increasing precorneal residence time, enhancing corneal permeation and lowering the systemic absorption of drug. Periocular injections and surgically implanted drug reservoirs could offer even greater duration of drug delivery, particularly when the drug is packaged within stable vehicles. Summary Novel platforms for providing sustained drug delivery in glaucoma continue to evolve. The ability to incorporate effective commercially available drugs into more stable compounds is an important element. Although more research is needed to establish their clinical efficacy, novel delivery systems will allow for more targeted medical therapy and for the opportunity to further explore neuroprotective and gene-based therapies.

Residual and Dynamic Range of Retinal Nerve Fiber Layer Thickness in Glaucoma: Comparison of Three OCT Platforms.

PURPOSE To estimate visual field (VF) sensitivity at which retinal nerve fiber layer (RNFL) thinning reaches the measurement floor and at which RNFL stops thinning (change points), the dynamic range of RNFL thickness, and the number of steps from normal to RNFL floor among three optical coherence tomography (OCT) devices. METHODS Glaucomatous patients (n = 58) and healthy subjects (n = 55-60) prospectively underwent VF testing and RNFL thickness measurement with Cirrus, Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were estimated with simple linear regression (SLR) and Bayesian change point (BCP) analyses. The dynamic range and number of steps to RNFL floor were determined. RESULTS The average VF change points and corresponding residual thickness at the time RNFL stopped thinning were -22.2 dB and 57.0 μm (Cirrus), -25.3 dB and 49.2 μm (Spectralis), and -24.6 dB and 64.7 μm (RTVue). The RNFL dynamic ranges derived from SLR values were wider on Spectralis (52.6 μm) than on Cirrus (35.4 μm) and RTVue (35.5 μm); the corresponding number of steps to reach the RNFL floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue. CONCLUSIONS The relative VF sensitivity at which average RNFL thickness reaches the measurement floor, the residual layer thickness, and RNFL dynamic measurement range differ among the three devices. However, the number of steps from normal to the RNFL thickness floor is comparable.

Determinants of Self-Reported Barriers to Glaucoma Medicine Administration and Adherence A Multisite Study

Background: Many factors influence glaucoma medication adherence. A better understanding of the relationships between health literacy, depressive symptoms, and patient-reported problems in using glaucoma medications may reveal opportunities for intervention that could improve patients’ clinical outcomes. Objective: To examine the relationship between patient characteristics (demographics, health literacy, and depressive symptoms) and patient-reported problems in using glaucoma medications and to assess factors related to patients’ self-reported adherence to glaucoma medications. Methods: Patients diagnosed with primary open-angle glaucoma (n = 228) currently taking intraocular pressure–lowering medications were recruited at 6 ophthalmology clinics. Patients were interviewed to identify problems using glaucoma medications, and self-reported medication adherence was determined using a Visual Analog Scale. Questionnaires were administered to assess health literacy, depressive symptoms, outcome expectations, and medication self-efficacy. Results: Younger patients (P = 0.03), patients with depressive symptoms (P = 0.02), and patients who reported more medication problems (P = 0.005) were significantly less adherent to their glaucoma medications. Patients with higher glaucoma medication self-efficacy adherence scores (P = 0.003) and higher outcome expectations (P = 0.03) were significantly more adherent. Conclusions: Providers should consider using tools to screen glaucoma patients for depressive symptoms and for problems in using medications to identify patients who are at higher risk of nonadherence to treatment and who might benefit from follow-up with primary care providers.

The Risk of Intraocular Pressure Elevation in Pediatric Noninfectious Uveitis.

PURPOSE To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric noninfectious uveitis. DESIGN Multicenter retrospective cohort study. PARTICIPANTS Nine hundred sixteen children (1593 eyes) younger than 18 years at presentation with noninfectious uveitis followed up between January 1978 and December 2007 at 5 academic uveitis centers in the United States. METHODS Medical records review by trained, certified experts. MAIN OUTCOME MEASURES Prevalence and incidence of IOP of 21 mmHg or more and 30 mmHg or more and incidence of a rise in IOP by 10 mmHg or more. To avoid underascertainment, outcomes were counted as present when IOP-lowering therapies were in use. RESULTS Initially, 251 (15.8%) and 46 eyes (2.9%) had IOP ≥21 mmHg and ≥30 mmHg, respectively. Factors significantly associated with presenting IOP elevation included age of 6 to 12 years (versus other pediatric ages), prior cataract surgery, pars plana vitrectomy, duration of uveitis ≥6 months, contralateral IOP elevation, presenting visual acuity worse than 20/40, and topical corticosteroid use (in a dose-response relationship). The median follow-up was 1.25 years (interquartile range, 0.4-3.66). The estimated incidence of any observed IOP elevation to ≥21 mmHg, to ≥30 mmHg, and increase in IOP by ≥10 mmHg was 33.4%, 14.8%, and 24.4%, respectively, within 2 years. Factors associated with IOP elevation included pars plana vitrectomy, contralateral IOP elevation (adjusted hazard ratio [aHR], up to 9.54; P < 0.001), and the use of topical (aHR, up to 8.77 that followed a dose-response relationship; P < 0.001), periocular (aHR, up to 7.96; P < 0.001), and intraocular (aHR, up to 19.7; P < 0.001) corticosteroids. CONCLUSIONS Intraocular pressure elevation affects a large minority of children with noninfectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with noninfectious uveitis should be followed up closely for IOP elevation, especially when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present.

Patient Question-Asking About Glaucoma and Glaucoma Medications During Videotaped Medical Visits

We applied the ecologic model of communication in medical consultations to examine how patient, physician, and situational/contextual factors are associated with whether patients ask one or more questions about glaucoma and glaucoma medications during visits to ophthalmologists. Patients with glaucoma who were newly prescribed or already on glaucoma medications were recruited at six ophthalmology clinics. Patients’ visits with their doctors were video-recorded and patients were interviewed after visits. Generalized estimating equations were used to analyze the data. Two hundred and seventy-nine patients participated. Patients asked one or more questions about glaucoma during 59% of visits and about glaucoma medications during 48% of visits. Patients who were newly prescribed glaucoma medications were significantly more likely to ask one or more questions about glaucoma and glaucoma medications. Whether providers asked patients if they had questions was not significantly associated with patient question-asking. Patients were significantly more likely to ask older providers questions about glaucoma medications and female providers questions about glaucoma. Eye care providers should encourage glaucoma patients to ask questions during their medical visits.

The Effect of Eye Drop Technique Education in Patients With Glaucoma

ABSTRACT Education about how to administer eye drops may improve a patient’s ability to instill his or her eye drops correctly. Our objectives were to (a) document the methods providers use to educate glaucoma patients about eye drop technique; (b) determine whether eye drop technique education varies by provider and patient characteristics; and (c) evaluate whether education predicts improved patient technique. We conducted an 8-month longitudinal study of 279 glaucoma patients and 15 providers in which we recorded on videotape the content of glaucoma office visits at two time points (baseline and 4- to 6-week follow-up) and videotaped patient eye drop technique at three time points (baseline, 4- to 6-week follow-up, and 8-month follow-up). Mann–Whitney rank sum tests were used to determine whether education was associated with improved patient eye drop technique over time. Ninety-four patients (34%) received technique education at either visit; 31% received verbal education and 10% received a technique demonstration. Only 24 patients (47%) who were new to eye drops received technique education at the baseline visit. Patients who were new to drops at baseline (p = .008) and patients who asked a question about drops (p < .001) were more likely to receive technique education. Education was not associated with improved technique. Eye drop technique education occurs infrequently during glaucoma office visits. Future studies should compare the effectiveness of different educational methods, such as patient demonstration versus provider verbal instruction, to determine which method is best at improving patient eye drop technique.