Visual Field Progression in Glaucoma What Is the Specificity of the Guided Progression Analysis?

Purpose: To estimate the specificity of the Guided Progression Analysis (GPA) (Carl Zeiss Meditec, Dublin, CA) in individual patients with glaucoma. Design: Observational cohort study. Participants: Thirty patients with open-angle glaucoma. Methods: In 30 patients with open-angle glaucoma, 1 eye (median mean deviation [MD], −2.5 decibels [dB]; interquartile range, −4.4 to −1.3 dB) was tested 12 times over 3 months (Humphrey Field Analyzer, Carl Zeiss Meditec; SITA Standard, 24-2). “Possible progression” and “likely progression” were determined with the GPA. These analyses were repeated after the order of the tests had been randomly rearranged (1000 unique permutations). Main Outcome Measures: Rate of false-positive alerts of “possible progression” and “likely progression” with the GPA. Results: On average, the specificity of the GPA “likely progression” alert was high—for the entire sample, the mean rate of false-positive alerts after 10 follow-up tests was 2.6%. With “possible progression,” the specificity was considerably lower (false-positive rate, 18.5%). Most important, the cumulative rate of false-positive alerts varied substantially among patients, from 0.31, P≤0.10). Conclusions: On average, progression criteria currently used in the GPA have high specificity, but some patients are more likely to show false-positive alerts than others. This is a natural consequence of population-based change criteria and may not matter in clinical trials and studies in which large groups of patients are compared. However, it must be considered when the GPA is used in clinical practice where specificity needs to be controlled for individual patients

Performing meta-analysis with incomplete statistical information in clinical trials

<p>Abstract</p> <p>Background</p> <p>Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM) about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis.</p> <p>Methods</p> <p>Both of our methods use the assumption that the samples for which the sampling distributions will be merged are randomly selected from the same population. In the prognostic method, we predict the missing SEMs from the given SEMs. In the interval method, we define intervals that we believe will contain the missing SEMs and then we use these intervals in the merging process.</p> <p>Results</p> <p>Two sets of clinical trials are used to verify our methods. One family of trials is on comparing different drugs for reduction of low density lipprotein cholesterol (LDL) for Type-2 diabetes, and the other is about the effectiveness of drugs for lowering intraocular pressure (IOP). Both methods are shown to be useful for approximating the conventional meta-analysis including trials with incomplete information. For example, the meta-analysis result of Latanoprost versus Timolol on IOP reduction for six months provided in <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> was 5.05 ± 1.15 (Mean ± SEM) with full information. If the last trial in this study is assumed to be with partial information, the traditional analysis method for dealing with incomplete information that ignores this trial would give 6.49 ± 1.36 while our prognostic method gives 5.02 ± 1.15, and our interval method provides two intervals as Mean ∈ [4.25, 5.63] and SEM ∈ [1.01, 1.24].</p> <p>Conclusion</p> <p>Both the prognostic and the interval methods are useful alternatives for dealing with missing data in meta-analysis. We recommend clinicians to use the prognostic method to predict the missing SEMs in order to perform meta-analysis and the interval method for obtaining a more cautious result.</p

Central corneal thickness and progression of the visual field and optic disc in glaucoma

Aims: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. Methods: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. Results: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression

Hypotony maculopathy after filtering surgery with mitomycin C. Incidence and treatment

Hypotony maculopathy after glaucoma filtering surgery with adjunctive mitomycin C has been reported to occur in 3% to 14% of cases. The authors evaluated its incidence when using a corneal safety-valve incisior intended to reduce its occurrence. The authors also evaluated a technique for reversing hypotony maculopathy by reoperation using two sets of stitches in the scleral flap, with one set tied tightly to temporarily raise the intraocular pressure, stretch the sclera, and flatten chorioretinal folds. The authors reviewed the results of 699 procedures performed between April 1991 and October 1994. All were performed or supervised by one surgeon (PFP). Hypotony maculopathy developed in 9 (1.3%) of 699 eyes. There was a statistically significant higher incidence in primary filters (4%) as compared to secondary filters or combined procedures. After revision, eight (89%) of nine recovered visual acuity of greater than or equal to 20/30 and the mean intraocular pressure was 14.5 +/- 4 mmHg at a mean follow-up of 15 months. The incidence of hypotony maculopathy after glaucoma filtering surgery with mitomycin C using a corneal safety-valve incision is less than that reported in the literature without this incision. There is an increased risk in myopes, young patients, and primary filters. Early intervention with the described scleral flap revision technique usually allows restoration of prefiltration visual acuity without compromise of bleb function

Visual field progression with frequency-doubling matrix perimetry and standard automated perimetry in patients with glaucoma and in healthy controls

Importance: A new analysis method called permutation of pointwise linear regression measures the significance of deterioration over time at each visual field location, combines the significance values into an overall statistic, and then determines the likelihood of change in the visual field. Because the outcome is a single P value, individualized to that specific visual field and independent of the scale of the original measurement, the method is well suited for comparing techniques with different stimuli and scales. Objective: To test the hypothesis that frequency-doubling matrix perimetry (FDT2) is more sensitive than standard automated perimetry (SAP) in identifying visual field progression in glaucoma. Design, Setting, and Participants: Patients with open-angle glaucoma and healthy controls were examined by FDT2 and SAP, both with the 24-2 test pattern, on the same day at 6-month intervals in a longitudinal prospective study conducted in a hospital-based setting. Only participants with at least 5 examinations were included. Intervention: Data were analyzed with permutation of pointwise linear regression. Main Outcome and Measure: Permutation of pointwise linear regression is individualized to each participant, in contrast to current analyses in which the statistical significance is inferred from population-based approaches. Analyses were performed with both total deviation and pattern deviation. Results: Sixty-four patients and 36 controls were included in the study. The median age, SAP mean deviation, and follow-up period were 65 years, −2.6 dB, and 5.4 years, respectively, in patients and 62 years, +0.4 dB, and 5.2 years, respectively, in controls. Using total deviation analyses, statistically significant deterioration was identified in 17% of patients with FDT2, in 34% of patients with SAP, and in 14% of patients with both techniques; in controls these percentages were 8% with FDT2, 31% with SAP, and 8% with both. Using pattern deviation analyses, statistically significant deterioration was identified in 16% of patients with FDT2, in 17% of patients with SAP, and in 3% of patients with both techniques; in controls these values were 3% with FDT2 and none with SAP. Conclusions and Relevance: No evidence was found that FDT2 is more sensitive than SAP in identifying visual field deterioration. In about one-third of healthy controls, age-related deterioration with SAP reached statistical significance

Laminar Displacement and Prelaminar Tissue Thickness Change after Glaucoma Surgery Imaged with Optical Coherence Tomography

PURPOSE. To study changes in lamina cribrosa position and prelaminar tissue thickness (PTT) after surgical IOP reduction in glaucoma patients. METHODS. Twenty-two patients (mean age, 71.4 years) were imaged with spectral domain optical coherence tomography (SD-OCT; 24 radial B-scans centered on the optic nerve head [ONH]) before trabeculectomy or tube shunt implantation. Follow up images were acquired 1 week, 1 month, 3 months, and 6 months postsurgery. Bruch's membrane opening (BMO), the internal limiting membrane (ILM) and the anterior laminar surface (ALS) were segmented in each radial scan with custom software. Surfaces were fitted to the ILM and ALS with the extracted three-dimesional coordinates. PTT was the distance between the ILM and ALS, perpendicular to a BMO reference plane. Serial postsurgical laminar displacement (LD), relative to the BMO reference plane, and changes in PTT were measured. Positive values indicated anterior LD. RESULTS. Mean (SD) presurgery IOP was 18.1 (6.5) mm Hg, and reduced by 4.7 (5.5), 2.4 (7.7), 7.0 (6.2), and 6.8 (7.5) mm Hg at 1 week, 1 month, 3 months, and 6 months postsurgery, respectively. At the four postsurgery time points, there was significant anterior LD (1.8 [9.5], -1.1 [8.9], 8.8 [20.2], and 17.9 [25.8] mu m) and PTT increase (1.7 [13.3], 2.4 [11.9], 17.4 [13.7], and 13.9 [18.6] mu m). LD was greater in ONHs with larger BMO area (P = 0.01) and deeper ALS (P = 0.04); however, PTT was not associated with any of the tested independent variables. CONCLUSIONS. Both anterior LD and thickening of prelaminar tissue occur after surgical IOP reduction in patients with glaucoma. (Invest Ophthalmol Vis Sci. 2012;53:5819-5826) DOI:10.1167/iovs.12-992