False negative results in glaucoma detection with Heidelberg Retina Tomograph II

Catherine Deghislage, Lidwine Van Malderen, Thierry G ZeyenDepartment of Ophthalmology, University Hospitals, Leuven, B-3000, BelgiumPurpose: To evaluate the rate of false negative results with the Heidelberg Retina Tomograph (HRT II) in a glaucoma practice.Design: Cross-sectional study.Methods: We analyzed the HRTs taken between October 2002 and October 2003 in our glaucoma clinic, and selected the patients who had a good quality image (SD < 40 µ) with a normal Moorfield’s Regression Analysis (MRA). A masked independent observer classified those patients as normal, glaucoma suspect, or glaucomatous on the basis of optic disc stereo photos (ODP) and at least 2 consecutive reliable automated perimetries. The diagnosis of glaucoma was based on a glaucomatous optic disc with a congruent, reproducible visual field defect.Results: Four hundred and fifty patients who had undergone an HRT examination were analyzed. One hundred and nine patients had an HRT classified as normal on the MRA, and a good quality image. Fifteen of those 109 patients (13.7%) were classified as glaucomatous on the basis of an abnormal ODP with corresponding visual field defect. Seven (6.4%) patients were classified as glaucoma suspect.Conclusion: Fourteen percent of glaucoma patients with glaucoma remained undetected with the HRT II Moorfield’s regression analysis as a sole means to detect glaucoma.Keywords: glaucoma detection, false negative results, Heidelberg Retina Tomograph I

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

Accuracy of matching optic discs with visual fields the european structure and function assessment trial (ESAFAT)

Purpose: To determine the ability of ophthalmologists across Europe to match stereoscopic optic disc photographs to visual fields of varying severity. Design: Evaluation and comparison of 2 diagnostic tests. Participants: A total of 109 of 260 invited ophthalmologists in 11 European countries. These had participated in the previous European Optic Disc Assessment Trial (EODAT), a trial on glaucoma diagnostic accuracy based on optic discs only. Methods: Each participant matched stereo optic disc photographs of 40 healthy and 48 glaucomatous eyes to a visual field chosen from 4 options per disc. The 4 presented visual fields included the corresponding one and 3 other visual fields, varying in severity. The matching accuracy and any inaccuracy per disease severity were calculated. Classification accuracy (as glaucomatous or healthy) was compared with EODAT data. Duplicate slides allowed for the assessment of intraobserver agreement. Main Outcome Measures: Accuracy of matching optic discs with their corresponding visual field and of classifying them as healthy or glaucomatous; intraobserver agreement (kappa). Results: The overall accuracy of ophthalmologists for correctly matching stereoscopic optic disc photographs to their visual fields was 58.7%. When incorrectly matched, the observers generally overestimated the visual field severity (P<0.001), notably in eyes with early glaucoma. The intraobserver agreement was, on average, moderate (0.52). Conclusions: European ophthalmologists correctly matched stereoscopic optic disc photographs to their corresponding visual field in only approximately 59% of cases. In most mismatches, the clinicians overestimated the visual field damage. (C) 2013 by the American Academy of Ophthalmology

Clinical assessment of stereoscopic optic disc photographs for glaucoma: the European Optic Disc Assessment Trial.

International audiencePURPOSE: To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists. DESIGN: Evaluation of diagnostic test and technology. PARTICIPANTS: A total of 243 of 875 invited ophthalmologists in 11 European countries. METHODS: We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers. MAIN OUTCOME MEASURES: Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa). RESULTS: The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRT's best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on average good (0.7). CONCLUSIONS: In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references

OCT Signal Enhancement with Deep Learning

Purpose- To establish whether deep learning methods are able to improve the signal-to-noise ratio of time-domain (TD) OCT images to approach that of spectral-domain (SD) OCT images. Design- Method agreement study and progression detection in a randomized, double-masked, placebo-controlled, multicenter trial for open-angle glaucoma (OAG), the United Kingdom Glaucoma Treatment Study (UKGTS). Participants- The training and validation cohort comprised 77 stable OAG participants with TD OCT and SD OCT imaging at up to 11 visits within 3 months. The testing cohort comprised 284 newly diagnosed OAG patients with TD OCT images from a cohort of 516 recruited at 10 United Kingdom centers between 2007 and 2010. Methods- An ensemble of generative adversarial networks (GANs) was trained on TD OCT and SD OCT image pairs from the training dataset and applied to TD OCT images from the testing dataset. Time-domain OCT images were converted to synthesized SD OCT images and segmented via Bayesian fusion on the output of the GANs. Main Outcome Measures- Bland-Altman analysis assessed agreement between TD OCT and synthesized SD OCT average retinal nerve fiber layer thickness (RNFLT) measurements and the SD OCT RNFLT. Analysis of the distribution of the rates of RNFLT change in TD OCT and synthesized SD OCT in the two treatment arms of the UKGTS was compared. A Cox model for predictors of time-to-incident visual field (VF) progression was computed with the TD OCT and the synthesized SD OCT images. Results- The 95% limits of agreement were between TD OCT and SD OCT were 26.64 to –22.95; between synthesized SD OCT and SD OCT were 8.11 to –6.73; and between SD OCT and SD OCT were 4.16 to –4.04. The mean difference in the rate of RNFLT change between UKGTS treatment and placebo arms with TD OCT was 0.24 (P = 0.11) and with synthesized SD OCT was 0.43 (P = 0.0017). The hazard ratio for RNFLT slope in Cox regression modeling for time to incident VF progression was 1.09 (95% confidence interval [CI], 1.02–1.21; P = 0.035) for TD OCT and 1.24 (95% CI, 1.08–1.39; P = 0.011) for synthesized SD OCT. Conclusions- Image enhancement significantly improved the agreement of TD OCT RNFLT measurements with SD OCT RNFLT measurements. The difference, and its significance, in rates of RNFLT change in the UKGTS treatment arms was enhanced and RNFLT change became a stronger predictor of VF progression