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

Live outflow imaging in porcine eyes

Purpose: Although outflow of aqueous humor can be estimated using fluorophotometry and tonography, no method exists to assess segmental outflow directly. This has hindered investigations into outflow resistance elements that are downstream of the trabecular meshwork and into causes of failure of canal-based minimally invasive glaucoma surgeries (MIGS). Here, we describe a method to observe and quantify conventional outflow directly in ex vivo whole eyes and an organotypic culture model using standard fluorescence visualization equipment. Results: Aqueous outflow paths could be distinguished from venous and arterial vessels. Intricate vascular tree filling patterns were observed down to estimated 50 micrometer diameter. Whole eyes demonstrated significantly earlier filling of the nasal (SN, IN) than of the temporal quadrants (ST, IT). The fastest, superonasal quadrant filled 1.6 times faster than the slowest, superotemporal quadrant (p≤0.05). The inferotemporal quadrant also filled faster than the superotemporal quadrant. In contrast, perfused anterior segment cultures had lost these characteristic filling time differences (p>0.05). One eye showed no outflow after 20 minutes of pressurization. After three days of culture, the same quadrant that was the fastest in whole eyes (SN), was 2.2 times as fast as the slowest (ST) but this did not reach statistical significance with the number of eyes tested. The eye without flow at 20 minutes did not recuperate during 3 days of culture. Reverse filling was occasionally seen in d3 anterior segments (bottom row, red arrowhead). Whole eyes could not be reliably cultured for 3 days. Discussion: Canalograms using a green fluorescent chromophore can be obtained with standard visualization equipment to estimate the local outflow function. Regionally different outflow patterns and filling times can be observed that match channel size equivalents in human eyes. Outflow is impaired in fresh anterior segment cultures but then normalizes to the pattern seen in whole eyes. The nasally increased flow may have implications for placement and study of MIGS

A feature agnostic approach for glaucoma detection in OCT volumes

Optical coherence tomography (OCT) based measurements of retinal layer thickness, such as the retinal nerve fibre layer (RNFL) and the ganglion cell with inner plexiform layer (GCIPL) are commonly used for the diagnosis and monitoring of glaucoma. Previously, machine learning techniques have utilized segmentation-based imaging features such as the peripapillary RNFL thickness and the cup-to-disc ratio. Here, we propose a deep learning technique that classifies eyes as healthy or glaucomatous directly from raw, unsegmented OCT volumes of the optic nerve head (ONH) using a 3D Convolutional Neural Network (CNN). We compared the accuracy of this technique with various feature-based machine learning algorithms and demonstrated the superiority of the proposed deep learning based method. Logistic regression was found to be the best performing classical machine learning technique with an AUC of 0.89. In direct comparison, the deep learning approach achieved a substantially higher AUC of 0.94 with the additional advantage of providing insight into which regions of an OCT volume are important for glaucoma detection. Computing Class Activation Maps (CAM), we found that the CNN identified neuroretinal rim and optic disc cupping as well as the lamina cribrosa (LC) and its surrounding areas as the regions significantly associated with the glaucoma classification. These regions anatomically correspond to the well established and commonly used clinical markers for glaucoma diagnosis such as increased cup volume, cup diameter, and neuroretinal rim thinning at the superior and inferior segments.Comment: 13 pages,3 figure

Glaucoma surgery calculator: limited additive IOP effect of phacoemulsification on Ab Interno Trabeculectomy

Purpose: To compare reduction of intraocular pressure (IOP) after Trabectome in pseudophakic patients and Trabectome combined with phacoemulsification (Trabectome-phaco) in phakic patients. Methods: Cases were excluded if patients were followed for less than 12 months, diagnosed with neovascular glaucoma, or required additional glaucoma surgery within 12 months after Trabectome or Trabectome-phaco. Missing data such as type of glaucoma, gender, or age was imputed by generating 5 similar but non-identical datasets. Groups were matched using Coarsened Exact Matching based on age, gender, type of glaucoma, race, preoperative number of glaucoma medications and baseline IOP. Linear regression was used to examine IOP reduction after surgery. Results: A total of 612 cases were included in the study with 248 Trabectome cases and 364 Trabectome-phaco cases. Baseline IOP was found to be statistically significant. An average of 0.73±0.03 mmHg IOP reduction is associated with an increment of 1 mmHg in baseline IOP. Type of surgery was not statistically significant after adjusting for baseline IOP, age, baseline number of glaucoma medications and type of glaucoma. Conclusion: Patients with higher baseline IOP are expected to have a greater IOP reduction

Stratification of phaco-trabectome surgery results using a glaucoma severity index

The outcomes of phacoemulsification combined with trabectome surgery was analyzed using a glaucoma severity index based on preoperative intraocular pressure (IOP), number of preoperative medications, and visual field damage. Despite a less absolute indication to lower IOP, a substantial pressure reduction was seen in patients with more advanced glaucoma

Documentation of Intraretinal Retinal Pigment Epithelium Migration via High-Speed Ultrahigh-Resolution Optical Coherence Tomography

Purpose To describe the features of intraretinal retinal pigment epithelium (RPE) migration documented on a prototype spectral-domain, high-speed, ultrahigh-resolution optical coherence tomography (OCT) device in a group of patients with early to intermediate dry age-related macular degeneration (AMD) and to correlate intraretinal RPE migration on OCT to RPE pigment clumping on fundus photographs. Design Retrospective, noncomparative, noninterventional case series. Participants Fifty-five eyes of 44 patients seen at the New England Eye Center between December 2007 and June 2008 with early to intermediate dry AMD. Methods Three-dimensional OCT scan sets from all patients were analyzed for the presence of intraretinal RPE migration, defined as small discreet hyperreflective and highly backscattering lesions within the neurosensory retina. Fundus photographs also were analyzed to determine the presence of RPE pigment clumping, defined as black, often spiculated, areas of pigment clumping within the macula. The en face OCT images were correlated with fundus photographs to demonstrate correspondence of intraretinal RPE migration on OCT and RPE clumping on fundus photography. Main Outcome Measures Drusen, dry AMD, intraretinal RPE migration, and RPE pigment clumping. Results On OCT scans, 54.5% of eyes (61.4% of patients) demonstrated intraretinal RPE migration. Of the fundus photographs, 56.4% demonstrated RPE pigment clumping. All eyes with intraretinal RPE migration on OCT had corresponding RPE pigment clumping on fundus photographs. The RPE pigment migrated most frequently into the outer nuclear layer (66.7% of eyes) and less frequently into more anterior retinal layers. Intraretinal RPE migration mainly occurred above areas of drusen (73.3% of eyes). Conclusions The appearance of intraretinal RPE migration on OCT is a common occurrence in early to intermediate dry AMD, occurring in 54.5% of eyes, or 61.4% of patients. The area of intraretinal RPE migration on OCT always correlated to areas of pigment clumping on fundus photography. Conversely, all but 1 eye with RPE pigment clumping on fundus photography also had areas of intraretinal RPE migration on OCT. The high incidence of intraretinal RPE migration observed above areas of drusen suggests that drusen may play physical and catalytic roles in facilitating intraretinal RPE migration in dry AMD patients.National Institutes of Health (U.S.) (Contract RO1-EY11289-23)National Institutes of Health (U.S.) (Contract R01-EY13178-07)National Institutes of Health (U.S.) (Contract R01-EY013516-07)United States. Air Force Office of Scientific Research (FA9550-07-1-0101)United States. Air Force Office of Scientific Research (FA9550-07-1-0014

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma

Purpose: To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Methods: Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Results: Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score ± SD in nonglaucomatous eyes was 1.3 ± 0.8 in control and 0.8 ± 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 ± 0.7 in control and 0.9 ± 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Conclusions: Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes. © 2009 Chang et al, publisher and licensee Dove Medical Press Ltd

Assessment of Artifacts and Reproducibility across Spectral- and Time-Domain Optical Coherence Tomography Devices

Purpose To report the frequency of optical coherence tomography (OCT) scan artifacts and to compare macular thickness measurements, interscan reproducibility, and interdevice agreeability across 3 spectral-domain (SD) OCT (also known as Fourier domain; Cirrus HD-OCT, RTVue-100, and Topcon 3D-OCT 1000) devices and 1 time-domain (TD) OCT (Stratus OCT) device. Design Prospective, noncomparative, noninterventional case series. Participants Fifty-two patients seen at the New England Eye Center, Tufts Medical Center Retina Service, between February and August 2008. Methods Two scans were performed for each of the SD OCT protocols: Cirrus macular cube 512×128 (software version 3.0; Carl Zeiss Meditec, Inc., Dublin, CA), RTVue (E)MM5 and MM6 (software version 3.5; Optovue, Inc., Fremont, CA), Topcon 3D Macular and Radial (software version 2.12; Topcon, Inc., Paramus, NJ), in addition to 1 TD OCT scan via Stratus macular thickness protocol (software version 4.0; Carl Zeiss Meditec, Inc.). Scans were inspected for 6 types of OCT scan artifacts and were analyzed. Interscan reproducibility and interdevice agreeability were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots, respectively. Main Outcome Measures Optical coherence tomography image artifacts, macular thickness, reproducibility, and agreeability. Results Time-domain OCT scans contained a significantly higher percentage of clinically significant improper central foveal thickness (IFT) after manual correction (11-μm change or more) compared with SD OCT scans. Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT (11.1%) compared with the other SD OCT devices (Topcon 3D, 20.4%; Topcon Radial, 29.6%; RTVue (E)MM5, 42.6%; RTVue MM6, 24.1%; P = 0.001). All 3 SD OCT devices had central foveal subfield thicknesses that were significantly more than that of TD OCT after manual correction (P<0.0001). All 3 SD OCT devices demonstrated a high degree of reproducibility in the central foveal region (ICCs, 0.92–0.97). Bland-Altman plots showed low agreeability between TD and SD OCT scans. Conclusions Out of all OCT devices analyzed, cirrus HD-OCT scans exhibited the lowest occurrence of any artifacts (68.5%), IFT (40.7%), and clinically significant IFT (11.1%), whereas Stratus OCT scans exhibited the highest occurrence of clinically significant IFT. Further work on improving segmentation algorithm to decrease artifacts is warranted.Research to Prevent Blindness, Inc. (United States) (Challenge Grant)National Institutes of Health (U.S.) (Grant R01-EY11289-23)National Institutes of Health (U.S.) (Grant R01-EY13178-07)National Institutes of Health (U.S.) (Grant P30-EY008098)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0101)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0014

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