OCT for glaucoma diagnosis, screening and detection of glaucoma progression.

Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening

Optical Coherence Tomography Interpretation for Glaucoma

Structural glaucomatous changes occur more frequently in the earlier stages of glaucoma than functional defects so we should give special care on oct (optical coherence tomography) importance as the best current method. RNFL change detection are more useful in early glaucoma, GCC in moderate to advanced glaucoma while visual field test is more useful in advanced stages but overall using a combination of RNFL, ONH and macular measurement modalities is recommended for glaucoma evaluation because each of these parameters may be affected earlier than the others so, taking into account the findings from the RNFL, ONH and macula enhances early diagnosis of glaucoma

Three-Dimensional Spectral-Domain Optical Coherence Tomography Data Analysis for Glaucoma Detection

Purpose: To develop a new three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) data analysis method using a machine learning technique based on variable-size super pixel segmentation that efficiently utilizes full 3D dataset to improve the discrimination between early glaucomatous and healthy eyes. Methods: 192 eyes of 96 subjects (44 healthy, 59 glaucoma suspect and 89 glaucomatous eyes) were scanned with SD-OCT. Each SD-OCT cube dataset was first converted into 2D feature map based on retinal nerve fiber layer (RNFL) segmentation and then divided into various number of super pixels. Unlike the conventional super pixel having a fixed number of points, this newly developed variable-size super pixel is defined as a cluster of homogeneous adjacent pixels with variable size, shape and number. Features of super pixel map were extracted and used as inputs to machine classifier (LogitBoost adaptive boosting) to automatically identify diseased eyes. For discriminating performance assessment, area under the curve (AUC) of the receiver operating characteristics of the machine classifier outputs were compared with the conventional circumpapillary RNFL (cpRNFL) thickness measurements. Results: The super pixel analysis showed statistically significantly higher AUC than the cpRNFL (0.855 vs. 0.707, respectively, p = 0.031, Jackknife test) when glaucoma suspects were discriminated from healthy, while no significant difference was found when confirmed glaucoma eyes were discriminated from healthy eyes. Conclusions: A novel 3D OCT analysis technique performed at least as well as the cpRNFL in glaucoma discrimination and even better at glaucoma suspect discrimination. This new method has the potential to improve early detection of glaucomatous damage. © 2013 Xu et al

Risk Assessment of Ocular Hypertension and the Use of Medication

Ocular hypertension (OHT) is the only known modifiable risk factor of glaucoma development. Intraocular pressure (IOP)-lowering therapy reduces the risk of glaucoma development. The 5-year risk of glaucoma conversion is <10% for untreated OHT patients. Cost-effectiveness analyses suggested that it is not cost-effective to treat all patients with OHT. Treatment should be targeted towards the higher-risk group—namely, patients with older age, a higher level of IOP, a thinner central corneal thickness (CCT), a larger vertical cup-to-disc ratio (VCDR) and a smaller pattern standard deviation (PSD) value on visual field (VF) test. These risk factors were established by the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS). However, there is significant variability in the measurement of the currently known risk factors, especially if the assessment is taken from a longitudinal perspective. This can lead to overtreatment or under-treatment: the former exposing the patient to unnecessary side effects of IOP-lowering eye drops and the latter putting the patient at risk of developing glaucoma. The advancement of new VF algorithm and ocular imaging can lead to the identification of new approaches to risk stratification and, thus, more specific treatment for OHT patients

Role of Optical Coherence Tomography in the Evaluation and Management of Glaucoma

Glaucoma is the leading cause of irreversible, yet preventable, blindness throughout the world. Since it is a disease which can be treated but not cured, it is crucial for the treating ophthalmologist to catch the disease as early as possible. The diagnosis of glaucoma is currently based on the appearance of the optic disc and standard achromatic perimetry. However, to detect glaucoma in its early stages, there are various diagnostic modalities of which optical coherence tomography serves as a novel tool. Optical coherence tomography has emerged over the years with the ability to detect changes in the optic nerve head, retinal nerve fiber layer, and currently the ganglion cell layer much earlier than the defects manifest functionally. Thus, optical coherence tomography acts as an important diagnostic aid to diagnose and monitor the progression of this sight threatening disease called glaucoma

The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in Normal and Glaucoma Subjects.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P &lt; 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P &gt; 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH

Optic nerve head and fibre layer imaging for diagnosing glaucoma

Background The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma. Objectives To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage. Search methods We searched several databases for this review. The most recent searches were on 19 February 2015. Selection criteria We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or Data collection and analysis We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level. Main results We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear. Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study. The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio. Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people. Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD &lt; -6 db versus 0.64 (0.60 to 0.69) for MD &gt;=-6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P &lt; 0.0001 for the difference in relative DOR). Authors' conclusions The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base. We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data

A Deep Learning Approach to Denoise Optical Coherence Tomography Images of the Optic Nerve Head

Purpose: To develop a deep learning approach to de-noise optical coherence tomography (OCT) B-scans of the optic nerve head (ONH). Methods: Volume scans consisting of 97 horizontal B-scans were acquired through the center of the ONH using a commercial OCT device (Spectralis) for both eyes of 20 subjects. For each eye, single-frame (without signal averaging), and multi-frame (75x signal averaging) volume scans were obtained. A custom deep learning network was then designed and trained with 2,328 "clean B-scans" (multi-frame B-scans), and their corresponding "noisy B-scans" (clean B-scans + gaussian noise) to de-noise the single-frame B-scans. The performance of the de-noising algorithm was assessed qualitatively, and quantitatively on 1,552 B-scans using the signal to noise ratio (SNR), contrast to noise ratio (CNR), and mean structural similarity index metrics (MSSIM). Results: The proposed algorithm successfully denoised unseen single-frame OCT B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean SNR increased from $4.02 \pm 0.68$ dB (single-frame) to $8.14 \pm 1.03$ dB (denoised). For all the ONH tissues, the mean CNR increased from $3.50 \pm 0.56$ (single-frame) to $7.63 \pm 1.81$ (denoised). The MSSIM increased from $0.13 \pm 0.02$ (single frame) to $0.65 \pm 0.03$ (denoised) when compared with the corresponding multi-frame B-scans. Conclusions: Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort

Eyes with Large Disc Cupping and Normal Intraocular Pressure: Using Optical Coherence Tomography to Discriminate Those With and Without Glaucoma

We evaluated the ability of spectral-domain optic coherence tomography (SD-OCT) to differentiate large physiological optic disc cupping (LPC) from glaucomatous cupping in eyes with intraocular pressure (IOP) within the normal range.  We prospectively enrolled patients with glaucoma or presumed LPC. Participants  had optic discs with confirmed or suspected glaucomatous damage (defined as a vertical cup-to-disc ratio≥0.6), and all eyes had known untreated IOP&lt;21 mmHg. For glaucomatous eyes, a reproducible glaucomatous visual field (VF) defect was required. LPC eyes required normal VF and no evidence of progressive glaucomatous neuropathy (follow-up≥30 months). Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses were obtained using SD-OCT. For all studied parameters of pRNFL and GCC thicknesses, eyes with glaucoma (n=36) had significantly thinner values compared to eyes with LPC (n=71; P&lt;0.05 for all comparisons). In addition, pRNFL parameters had sensitivity of 66.7% and specificity of 83.1%, and GCC parameters had sensitivity of 61.2% and specificity of 81.7%. The combination of the two analyses increased the sensitivity to 80.6%. In conclusion, while evaluating patients with large optic disc cupping and IOP in the statistically normal range, SD-OCT had only limited diagnostic ability to differentiate those with and without glaucoma. Although the diagnostic ability of the pRNFL and the GCC scans were similar, these parameters yielded an increase in sensitivity when combined, suggesting that both parameters could be considered simultaneously in these cases