Current Knowledge and Attitudes Concerning Cost-Effectiveness in Glaucoma Pharmacotherapy: A Glaucoma Specialists Focus Group Study.

Background:Rising healthcare costs motivate continued cost-reduction efforts. To help lower costs associated with open-angle glaucoma (OAG), a prevalent, progressive disease with substantial direct and indirect costs, clinicians need to understand the cost-effectiveness of intraocular pressure (IOP)-lowering pharmacotherapies. There is little published information on clinicians' knowledge and attitudes about cost-effectiveness in glaucoma treatment. Purpose:This pilot focus group study aimed to explore clinician attitudes and perspectives around the costs and cost drivers of glaucoma therapy; the implementation of cost-effectiveness decisions; the clinical utility of cost-effectiveness studies; and the cost-effectiveness of available treatments. Methods:Six US glaucoma specialists participated in two separate teleconferencing sessions (three participants each), managed by an independent, skilled moderator (also a glaucoma specialist) using a discussion guide. Participants reviewed recent publications (n=25) on health economics outcomes research in glaucoma prior to the sessions. Results:Participants demonstrated a clear understanding of the economic burden of glaucoma therapy and identified medications, diagnostics, office visits, and treatment changes as key cost drivers. They considered cost-effectiveness an appropriate component of treatment decision-making but identified the need for additional data to inform these decisions. Participants indicated that there were only a few recent studies on health economics outcomes in glaucoma which evaluate parameters important to patient care, such as quality of life and medication adherence, and that longitudinal data were scant. In addition to efficacy, participants felt patient adherence and side-effect profile should be included in economic evaluations of glaucoma pharmacotherapy. Recently approved medications were evaluated in this context. Conclusion:Clinicians deem treatment decisions based on cost-effectiveness data as clinically appropriate. Newer IOP-lowering therapies with potentially greater efficacy and favorable side-effect and adherence profiles may help optimize cost-effectiveness. Future studies should include: clinicians' perspectives; lack of commercial bias; analysis of long-term outcomes/costs; more comprehensive parameters; real-world (including quality-of-life) data; and a robust Markov model

Structural Change Can Be Detected in Advanced-Glaucoma Eyes.

PurposeTo compare spectral-domain optical coherence tomography (SD-OCT) standard structural measures and a new three-dimensional (3D) volume optic nerve head (ONH) change detection method for detecting change over time in severely advanced-glaucoma (open-angle glaucoma [OAG]) patients.MethodsThirty-five eyes of 35 patients with very advanced glaucoma (defined as a visual field mean deviation < -21 dB) and 46 eyes of 30 healthy subjects to estimate aging changes were included. Circumpapillary retinal fiber layer thickness (cpRNFL), minimum rim width (MRW), and macular retinal ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured using the San Diego Automated Layer Segmentation Algorithm (SALSA). Progression was defined as structural loss faster than 95th percentile of healthy eyes. Three-dimensional volume ONH change was estimated using the Bayesian-kernel detection scheme (BKDS), which does not require extensive retinal layer segmentation.ResultsThe number of progressing glaucoma eyes identified was highest for 3D volume BKDS (13, 37%), followed by GCPIL (11, 31%), cpRNFL (4, 11%), and MRW (2, 6%). In advanced-OAG eyes, only the mean rate of GCIPL change reached statistical significance, -0.18 μm/y (P = 0.02); the mean rates of cpRNFL and MRW change were not statistically different from zero. In healthy eyes, the mean rates of cpRNFL, MRW, and GCIPL change were significantly different from zero. (all P < 0.001).ConclusionsGanglion cell-inner plexiform layer and 3D volume BKDS show promise for identifying change in severely advanced glaucoma. These results suggest that structural change can be detected in very advanced disease. Longer follow-up is needed to determine whether changes identified are false positives or true progression

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors

Risk Factors for Optic Disc Hemorrhage in the Low-Pressure Glaucoma Treatment Study

PurposeTo investigate risk factors for disc hemorrhage detection in the Low-Pressure Glaucoma Treatment Study.DesignCohort of a randomized, double-masked, multicenter clinical trial.MethodsLow-Pressure Glaucoma Treatment Study patients with at least 16 months of follow-up were included. Exclusion criteria included untreated intraocular pressure (IOP) of more than 21 mm Hg, visual field mean deviation worse than −16 dB, or contraindications to study medications. Patients were randomized to topical treatment with timolol 0.5% or brimonidine 0.2%. Stereophotographs were reviewed independently by 2 masked graders searching for disc hemorrhages. The main outcomes investigated were the detection of disc hemorrhage at any time during follow-up and their recurrence. Ocular and systemic risk factors for disc hemorrhage detection were analyzed using the Cox proportional hazards model and were tested further for independence in a multivariate model.ResultsTwo hundred fifty-three eyes of 127 subjects (mean age, 64.7 ± 10.9 years; women, 58%; European ancestry, 71%) followed up for an average ± standard deviation of 40.6 ± 12 months were included. In the multivariate analysis, history of migraine (hazard ratio [HR], 5.737; P = .012), narrower neuroretinal rim width at baseline (HR, 2.91; P = .048), use of systemic β-blockers (HR, 5.585; P = .036), low mean systolic blood pressure (HR, 1.06; P = .02), and low mean arterial ocular perfusion pressure during follow-up (HR, 1.172; P = .007) were significant and independent risk factors for disc hemorrhage detection. Treatment randomization was not associated with either the occurrence or recurrence of disc hemorrhages.ConclusionsIn this cohort of Low-Pressure Glaucoma Treatment Study patients, migraine, baseline narrower neuroretinal rim width, low systolic blood pressure and mean arterial ocular perfusion pressure, and use of systemic β-blockers were risk factors for disc hemorrhage detection. Randomization assignment did not influence the frequency of disc hemorrhage detection

Association of severity of primary open-angle glaucoma with serum vitamin D levels in patients of African descent.

PurposeTo study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels.MethodsA subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t-test.ResultsThe 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508).ConclusionsIn this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

Purpose: To investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs. Methods: 112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs. Result: 47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect. Conclusion: The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect

Glaucomatous Patterns in Frequency Doubling Technology (FDT) Perimetry Data Identified by Unsupervised Machine Learning Classifiers

Purpose: The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters. Methods: FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age. Results: FDT mean deviation was -1.00 dB (S.D. = 2.80 dB) and -5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p&lt;0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G(1) and G(2) combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G(1) and G(2) the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity. Conclusions: VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.open0

Performance of Deep Learning Architectures and Transfer Learning for Detecting Glaucomatous Optic Neuropathy in Fundus Photographs

The ability of deep learning architectures to identify glaucomatous optic neuropathy (GON) in fundus photographs was evaluated. A large database of fundus photographs (n = 14,822) from a racially and ethnically diverse group of individuals (over 33% of African descent) was evaluated by expert reviewers and classified as GON or healthy. Several deep learning architectures and the impact of transfer learning were evaluated. The best performing model achieved an overall area under receiver operating characteristic (AUC) of 0.91 in distinguishing GON eyes from healthy eyes. It also achieved an AUC of 0.97 for identifying GON eyes with moderate-to-severe functional loss and 0.89 for GON eyes with mild functional loss. A sensitivity of 88% at a set 95% specificity was achieved in detecting moderate-to-severe GON. In all cases, transfer improved performance and reduced training time. Model visualizations indicate that these deep learning models relied on, in part, anatomical features in the inferior and superior regions of the optic disc, areas commonly used by clinicians to diagnose GON. The results suggest that deep learning-based assessment of fundus images could be useful in clinical decision support systems and in the automation of large-scale glaucoma detection and screening programs