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1.  Spectral Domain Optical Coherence Tomography for Glaucoma (An AOS Thesis) 
Optical coherence tomography (OCT) is a rapidly evolving, robust technology that has profoundly changed the practice of ophthalmology. Spectral domain OCT (SD-OCT) increases axial resolution 2- to 3-fold and scan speed 60- to 110-fold vs time domain OCT (TD-OCT). SD-OCT enables novel scanning, denser sampling, and 3-dimensional imaging. This thesis tests my hypothesis that SD-OCT improves reproducibility, sensitivity, and specificity for glaucoma detection.
OCT progress is reviewed from invention onward, and future development is discussed. To test the hypothesis, TD-OCT and SD-OCT reproducibility and glaucoma discrimination are evaluated. Forty-one eyes of 21 subjects (SD-OCT) and 21 eyes of 21 subjects (TD-OCT) are studied to test retinal nerve fiber layer (RNFL) thickness measurement reproducibility. Forty eyes of 20 subjects (SD-OCT) and 21 eyes of 21 subjects (TD-OCT) are investigated to test macular parameter reproducibility. For both TD-OCT and SD-OCT, 83 eyes of 83 subjects are assessed to evaluate RNFL thickness and 74 eyes of 74 subjects to evaluate macular glaucoma discrimination.
Compared to conventional TD-OCT, SD-OCT had statistically significantly better reproducibility in most sectoral macular thickness and peripapillary RNFL sectoral measurements. There was no statistically significant difference in overall mean macular or RNFL reproducibility, or between TD-OCT and SD-OCT glaucoma discrimination. Surprisingly, TD-OCT macular RNFL thickness showed glaucoma discrimination superior to SD-OCT.
At its current development state, SD-OCT shows better reproducibility than TD-OCT, but glaucoma discrimination is similar for TD-OCT and SD-OCT. Technological improvements are likely to enhance SD-OCT reproducibility, sensitivity, specificity, and utility, but these will require additional development.
PMCID: PMC2646438  PMID: 19277249
2.  OCT for glaucoma diagnosis, screening and detection of glaucoma progression 
The British Journal of Ophthalmology  2013;98(Suppl 2):ii15-ii19.
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.
PMCID: PMC4208340  PMID: 24357497
3.  Detection of Macular Ganglion Cell Loss in Glaucoma by Fourier-Domain Optical Coherence Tomography 
Ophthalmology  2009;116(12):2305-2314.e2.
To map ganglion cell complex thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis.
Observational, cross-sectional study.
One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into three groups: 65 persons in the normal group (N), 78 in the perimetric glaucoma group (PG), and 52 in the pre-perimetric glaucoma group (PPG).
The RTVue FD-OCT system was used to map the macula over a 7×6 mm region. The macular OCT images were exported for automatic segmentation using software we developed. The program measured macular retinal (MR) thickness and ganglion cell complex (GCC) thickness. The GCC was defined as the combination of nerve fiber, ganglion cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and the diagnostic power of pattern-based diagnostic parameters were investigated. Results were compared to time-domain (TD) Stratus OCT measurements of MR and circumpapillary nerve fiber layer (NFL) thickness.
Main Outcome Measures
Repeatability was assessed by intraclass correlation (ICC), pooled standard deviation, and coefficient of variation. Diagnostic power was assessed by the area under the receiver operator characteristic (AROC) curve. Measurements in the PG group were the primary measures of performance.
The FD-OCT measurements of MR and GCC averages had significantly better repeatability than TD-OCT measurements of MR and NFL averages. The FD-OCT GCC average had significantly (P=0.02) higher diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT & TD-OCT) in differentiating between PG and N. One GCC pattern parameter, global loss volume, had significantly higher AROC (0.92) than the overall average (P=0.01). The diagnostic powers of the best GCC parameters were statistically equal to TD-OCT NFL average.
The higher speed and resolution of FD-OCT improved the repeatability of macular imaging compared to standard TD-OCT. Ganglion cell mapping and pattern analysis improved diagnostic power. The improved diagnostic power of macular GCC imaging is on par with, and complementary to, peripapillary NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for tracking glaucoma progression.
PMCID: PMC2787911  PMID: 19744726
optical coherence tomography; glaucoma; imaging; image processing
4.  Optical Coherence Tomography for Age-Related Macular Degeneration and Diabetic Macular Edema 
Executive Summary
The purpose of this evidence-based review was to examine the effectiveness and cost-effectiveness of spectral-domain (SD) optical coherence tomography (OCT) in the diagnosis and monitoring of patients with retinal disease, specifically age-related macular degeneration (AMD) and diabetic macular edema (DME). Specifically, the research question addressed was:
What is the sensitivity and specificity of spectral domain OCT relative to the gold standard?
Clinical Need: Target Population and Condition
The incidence of blindness has been increasing worldwide. In Canada, vision loss in those 65 years of age and older is primarily due to AMD, while loss of vision in those 18 years of age and older is mainly due to DME. Both of these conditions are diseases of the retina, which is located at the back of the eye. At the center of the retina is the macula, a 5 mm region that is responsible for what we see in front of us, our ability to detect colour, and fine detail. Damage to the macula gives rise to vision loss, but early detection of asymptomatic disease may lead to the prevention or slowing of the vision loss process.
There are two main types of AMD, ‘dry’ and ‘wet’. Dry AMD is the more prevalent of the two, accounting for approximately 85% of cases and characterized by small deposits of extracellular material called “drusen” that build up in Bruch’s membrane of the eye. Central vision loss is gradual with blurring and eventual colour fading. Wet AMD is a less prevalent condition (15% of all AMD cases) but it accounts for 90% of severe cases. It’s characterized by the appearance of retinal fluid with vision loss due to abnormal blood vessels/leakage within weeks to months of diagnosis. In 2003, the Canadian National Institute for the Blind (CNIB) prevalence estimate for AMD was 1 million Canadians, including approximately 400,000 affected Ontarians. The incidence in 2003 was estimated to be 78,000 new cases in Canada, with approximately one-third of these cases arising in Ontario (n=26,000). Over the next 25 years, the number of new cases is expected to triple.
DME is caused by complications of diabetes mellitus, both Type 1 and Type 2. It is estimated that 1-in-4 persons with diabetes has this condition, though it occurs more frequently among those with type 2 diabetes. The condition is characterized by a swelling of the retina caused by leakage of blood vessels at the back of the eye. In early stages of the disease, vision may still be normal but it can degrade rapidly in later stages. In 2003, the CNIB prevalence estimate for DME was 0.5 million Canadians, with approximately 200,000 Ontarians affected. The incidence of DME is more difficult to ascertain; however, based on an annual incidence rate of 0.8% (for those 20 years of age or older) and the assumption that 1-in-4 persons with diabetes is affected, the incidence of DME in Ontario is estimated to be 21,000 new cases per year.
Optical Coherence Tomography
Prior to the availability of OCT, the standard of care in the diagnosis and/or monitoring of retinal disease was serial testing with fluorescein angiography (FA), biomicroscopy (BM), and stereo-fundus photography (SFP). Each of these is a qualitative measure of disease based on subjective evaluations that are largely dependent on physician expertise. OCT is the first quantitative visual test available for the diagnosis of eye disease. As such, it is allows for a more objective evaluation of the presence/absence of retinal disease and it is the only test that provides a measure of retinal thickness. The technology was developed at the Michigan Institute of Technology (MIT) in 1991 as a real-time imaging modality and is considered comparable to histology. It’s a light-wave based technology producing cross-sectional images with scan rates and resolution parameters that have greatly improved over the last 10 years. It’s also a non-invasive, non-contact visual test that requires just 3 to 5 minutes to assess both eyes.
There are two main types of OCT system, both licensed by Health Canada as class II devices. The original patent was based on a time domain (TD) system (available from 1995) that had an image rate of 100 to 400 scans per second and provided information for a limited view of the retina with a resolution in the range of 10 to 20 μm. The newer system, spectral domain (SD) OCT, has been available since 2006. Improvements with this system include (i) a faster scan speed of approximately 27,000 scans per second; (ii) the ability to scan larger areas of the retina by taking six scans radially-oriented 30 degrees from each other; (iii) increased resolution at 5μm; and (iv) ‘real-time registration,’ which was not previously available with TD.
The increased scan speed of SD systems enables the collection of additional real-time information on larger regions of the retina, thus, reducing the reliance on assumptions required for retinal thickness and volume estimates based on software algorithms. The faster scan speed also eliminates image distortion arising from patient movement (not previously possible with TD), while the improvement in resolution allows for clearer and more distinguishable retinal layers with the possibility of detecting earlier signs of disease. Real-time registration is a new feature of SD that enables the identification of specific anatomical locations on the retina, against which subsequent tests can be evaluated. This is of particular importance in the monitoring of patients. In the evaluation of treatment effects, for example, this enables the same anatomic retinal location to be identified at each visit.
Literature Search
A literature search was performed on February 13, 2009 using Ovid MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 2003 to February 2009. The subject headings and keywords searched included AMD, DME, and OCT (the detailed search strategy can be viewed in Appendix 1). Excluded were case reports, comments, editorials, non-systematic reviews, and letters. Abstacts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. In total, 542 articles were included for review.
English-language articles and health technology assessments.
RCTs and observational studies of OCT and AMD or DME.
Studies focusing on either diagnosis or monitoring of disease.
Studies in which outcomes were not specific to those of interest in this report.
Studies of pediatric populations.
Studies on OCT as a screening tool.
Studies that did not assess comparative effectiveness of OCT with a referent, as specified below in “Comparisons of Interest”.
Outcomes of Interest
Studies of sensitivity, specificity.
Comparisons of Interest
Evidence exists for the following comparisons of interest:
OCT compared with the reference “fluorescein angiography” for AMD.
OCT compared with the reference “biomicroscopy” or “stereo or fundus photography” for DME.
Summary of Existing Evidence
No evidence for the accuracy of SD OCT compared to either FA, BM or SFP was published between January 2006 to February 2009; however, two technology assessments were found, one from Alberta and the other from Germany, both of which contain evidence for TD OCT. Although these HTAs included eight studies each, only one study from each report was specific to this review. Additionally, one systematic review was identified for OCT and DME. It is these three articles, all pertaining to time and not spectral domain OCT, as well as comments from experts in the field of OCT and retinal disease, that comprise the evidence contained in this review.
Upon further assessment and consultations with experts in the methodology of clinical test evaluation, it was concluded that these comparators could not be used as references in the evaluation of OCT. The main conclusion was that, without a third test as an arbiter, it is not possible to directly compare the sensitivity and specificity of OCT relative to either FA for AMD and stereo- or fundus – photography for DME. Therefore, in the absence of published evidence, it was deemed appropriate to consult a panel of experts for their views and opinions on the validity of OCT and its utility in clinical settings. This panel consisted of four clinicians with expertise in AMD and/or DME and OCT, as well as a medical biophysicist with scientific expertise in ocular technologies. This is considered level 5 evidence, but in the absence of an appropriate comparator for further evaluation of OCT, this may be the highest level of evidence possible.
Summary of Findings
The conclusions for SD OCT based on Level 5 evidence, or expert consultation, are as follows:
OCT is considered an essential part of the diagnosis and follow-up of patients with DME and AMD.
OCT is adjunctive to FA for both AMD and DME but should decrease utilization of FA as a monitoring modality.
OCT will result in a decline in the use of BM in the monitoring of patients with DME, given its increased accuracy and consistency.
OCT is diffusing rapidly and the technology is changing. Since FA is still considered pivotal in the diagnosis and treatment of AMD and DME, and there is no common outcome against which to compare these technologies, it is unlikely that RCT evidence of efficacy for OCT will ever be forthcoming.
In addition to the accuracy of OCT in the detection of disease, assessment of the clinical utility of this technology included a rapid review of treatment effects for AMD and DME. The treatment of choice for AMD is Lucentis®, with or without Avastin® and photodynamic therapy. For DME the treatment of choice is laser photocoagulation, which may be replaced with Lucentis® injections (Expert consultation). The evidence, as presented in systematic reviews and other health technology assessments, indicates that there are effective treatments available for both AMD and DME.
Considerations for the Ontario Health System
OCT testing is presently an uninsured service in Ontario with patients paying approximately $150 out-of-pocket per test. Several provinces do provide funding for this procedure, including British Columbia, Alberta, Saskatchewan, Newfoundland, Nova Scotia, Prince Edward Island, and the Yukon Territory. Provinces that do not provide such funding are Quebec, Manitoba and New Brunswick.
The demand for OCT is expected to increase with aging of the population.
PMCID: PMC3377511  PMID: 23074517
5.  Macula assessment using optical coherence tomography for glaucoma diagnosis 
The British journal of ophthalmology  2012;96(12):1452-1455.
Optical coherence tomography (OCT) is an interferometry-based imaging modality that generates high-resolution cross-sectional images of the retina. Circumpapillary retinal nerve fiber layer (cpRNFL) and optic nerve head assessments are the mainstay of glaucomatous structural measurements in OCT. However, because these measurements are not always available or precise, it would be useful to have another reliable indicator. The macula has been suggested as an alternative scanning location for glaucoma diagnosis. Using time-domain (TD-) OCT, macular measurements have shown to provide good glaucoma diagnostic capabilities. With the adoption of spectral-domain OCT, which allows a higher image resolution than TD-OCT, segmentation of inner macular layers becomes possible. These layers are specifically prone to glaucomatous damage and thickness measurements show a comparable performance to that of glaucomatous cpRNFL measurements. The role of macular measurements for detection of glaucoma progression is still under investigation. More sophisticated measurement and analysis tools that can amplify the advantages of macular measurements are expected. For example, improvement of image quality would allow better visualization, development of various scanning modes would optimize macular measurements, and further refining of the analytical algorithm would provide more accurate segmentation. With these achievements, macular measurement can be an important surrogate for glaucomatous structural assessment.
PMCID: PMC3718015  PMID: 23018425
6.  Assessment of Artifacts and Reproducibility across Spectral and Time Domain Optical Coherence Tomography Devices 
Ophthalmology  2009;116(10):1960-1970.
To report the frequency of optical coherence tomography (OCT) scan artifacts and compare macular thickness measurements, inter-scan reproducibility and inter-device agreeability across three spectral / Fourier domain (SD) OCTs (Cirrus HD-OCT, RTVue-100 and Topcon 3D-OCT 1000) and one time domain (TD) OCT (Stratus OCT).
Prospective, non-comparative, non-interventional case series.
52 patients seen at New England Eye Center, Tufts Medical Center retina service between February and August 2008.
Two scans were performed for each of the SD-OCT protocols: Cirrus macular cube 512×128, RTVue (E)MM5 and MM6, Topcon 3D macular and radial, in addition to one TD-OCT scan via Stratus macular thickness protocol. Scans were inspected for six types of OCT scan artifacts and analyzed. Inter-scan reproducibility and inter-device agreeability were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots, respectively.
OCT image artifacts, Macular thickness, Reproducibility, Agreeability.
TD-OCT scans contained a significantly higher percentage of clinically significant improper central foveal thickness (IFT) post-manual correction (greater than or equal to 11 μm change) compared to SD-OCT scans. Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT (11.1%) compared to 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 three SD-OCT had central foveal subfield thicknesses significantly greater than TD-OCT post manual correction (p< 0.0001). All 3 SD-OCT demonstrated a high degree of reproducibility in the central foveal region (ICC= 0.92 to 0.97). Bland-Altman plots showed low agreeability between TD- and SD-OCT scans.
Cirrus HD-OCT scans exhibited the lowest occurrence of any artifacts (68.5%), IFT (40.7%) and clinically significant IFT (11.1%) compared to all other OCT devices examined, while Stratus OCT scans exhibited the highest occurrence of clinically significant IFT compared to all 3 SD-OCT examined. Significant differences in macular thickness occurred among SD- and TD-OCT. All SD-OCT examined revealed high reproducibility in the central foveal subfield (ICC 0.92 to 0.97). Higher scan density and speed obtainable with SD-OCT appear to improve reproducibility. Although software breakdown occurred to a variable degree with different commercial OCT, further work on improving segmentation algorithm to decrease artifacts is warranted.
PMCID: PMC2757525  PMID: 19592109
7.  Three-dimensional Retinal Imaging with High-Speed Ultrahigh-Resolution Optical Coherence Tomography 
Ophthalmology  2005;112(10):1734-1746.
To demonstrate high-speed, ultrahigh-resolution, 3-dimensional optical coherence tomography (3D OCT) and new protocols for retinal imaging.
Ultrahigh-resolution OCT using broadband light sources achieves axial image resolutions of ~2 μm compared with standard 10-μm-resolution OCT current commercial instruments. High-speed OCT using spectral/Fourier domain detection enables dramatic increases in imaging speeds. Three-dimensional OCT retinal imaging is performed in normal human subjects using high-speed ultrahigh-resolution OCT. Three-dimensional OCT data of the macula and optic disc are acquired using a dense raster scan pattern. New processing and display methods for generating virtual OCT fundus images; cross-sectional OCT images with arbitrary orientations; quantitative maps of retinal, nerve fiber layer, and other intraretinal layer thicknesses; and optic nerve head topographic parameters are demonstrated.
Three-dimensional OCT imaging enables new imaging protocols that improve visualization and mapping of retinal microstructure. An OCT fundus image can be generated directly from the 3D OCT data, which enables precise and repeatable registration of cross-sectional OCT images and thickness maps with fundus features. Optical coherence tomography images with arbitrary orientations, such as circumpapillary scans, can be generated from 3D OCT data. Mapping of total retinal thickness and thicknesses of the nerve fiber layer, photoreceptor layer, and other intraretinal layers is demonstrated. Measurement of optic nerve head topography and disc parameters is also possible. Three-dimensional OCT enables measurements that are similar to those of standard instruments, including the StratusOCT, GDx, HRT, and RTA.
Three-dimensional OCT imaging can be performed using high-speed ultrahigh-resolution OCT. Three-dimensional OCT provides comprehensive visualization and mapping of retinal microstructures. The high data acquisition speeds enable high-density data sets with large numbers of transverse positions on the retina, which reduces the possibility of missing focal pathologies. In addition to providing image information such as OCT cross-sectional images, OCT fundus images, and 3D rendering, quantitative measurement and mapping of intraretinal layer thickness and topographic features of the optic disc are possible. We hope that 3D OCT imaging may help to elucidate the structural changes associated with retinal disease as well as improve early diagnosis and monitoring of disease progression and response to treatment.
PMCID: PMC1939719  PMID: 16140383
8.  High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography 
Ophthalmology  2006;113(11):2054.e1-2054.14.
To assess high-speed ultrahigh-resolution optical coherence tomography (OCT) image resolution, acquisition speed, image quality, and retinal coverage for the visualization of macular pathologies.
Retrospective cross-sectional study.
Five hundred eighty-eight eyes of 327 patients with various macular pathologies.
High-speed ultrahigh-resolution OCT images were obtained in 588 eyes of 327 patients with selected macular diseases. Ultrahigh-resolution OCT using Fourier/spectral domain detection achieves ~3-μm axial image resolutions, acquisition speeds of ~25 000 axial scans per second, and >3 times finer resolution and >50 times higher speed than standard OCT. Three scan protocols were investigated. The first acquires a small number of high-definition images through the fovea. The second acquires a raster series of high-transverse pixel density images. The third acquires 3-dimensional OCT data using a dense raster pattern. Three-dimensional OCT can generate OCT fundus images that enable precise registration of OCT images with the fundus. Using the OCT fundus images, OCT results were correlated with standard ophthalmoscopic examination techniques.
Main Outcome Measures
High-definition macular pathologies.
Macular holes, age-related macular degeneration, epiretinal membranes, diabetic retinopathy, retinal dystrophies, central serous chorioretinopathy, and other pathologies were imaged and correlated with ophthalmic examination, standard OCT, fundus photography, and fluorescein angiography, where applicable. High-speed ultrahigh-resolution OCT generates images of retinal pathologies with improved quality, more comprehensive retinal coverage, and more precise registration than standard OCT. The speed preserves retinal topography, thus enabling the visualization of subtle changes associated with disease. High-definition high-transverse pixel density OCT images improve visualization of photoreceptor and pigment epithelial morphology, as well as thin intraretinal and epiretinal structures. Three-dimensional OCT enables comprehensive retinal coverage, reduces sampling errors, and enables assessment of 3-dimensional pathology.
High-definition 3-dimensional imaging using high-speed ultrahigh-resolution OCT improves image quality, retinal coverage, and registration. This new technology has the potential to become a useful tool for elucidating disease pathogenesis and improving disease diagnosis and management.
PMCID: PMC1939823  PMID: 17074565
9.  Comparison of Automated Analysis of Cirrus HD-OCT™ Spectral Domain Optical Coherence Tomography with Stereo Photos of the Optic Disc 
Ophthalmology  2011;118(7):1348-1357.
To evaluate a new automated analysis of optic disc images obtained by spectral domain optical coherence tomography (SD-OCT). Areas of the optic disc, cup, and neural rim in SD-OCT images were compared with these areas from stereoscopic photographs, to represent the current traditional optic nerve evaluation. The repeatability of measurements by each method was determined and compared.
Evaluation of diagnostic technology.
119 healthy eyes, 23 eyes with glaucoma, and 7 suspect eyes
Optic disc and cup margins were traced from stereoscopic photographs by three individuals independently. Optic disc margins and rim widths were determined automatically in SD-OCT. A subset of photographs was examined and traced a second time, and duplicate SD-OCT images were also analyzed.
Agreement among photograph readers, between duplicate readings, and between SD-OCT and photographs were quantified by the intraclass correlation coefficient (ICC), by the root mean square (RMS), and the standard deviation (SD) of the differences.
Optic disc areas tended to be slightly larger when judged in photographs than by SD-OCT, while cup areas were similar. Cup and optic disc areas showed good correlation (0.8) between average photographic reading and SD-OCT, but only fair correlation of rim areas (0.4).
The SD-OCT was highly reproducible (ICC of 0.96 to 0.99). Each reader was also consistent with himself on duplicate readings of 21 photographs (ICC 0.80 to 0.88 for rim area, 0.95 to 0.98 for all other measurements), but reproducibility was not as good as SD-OCT. Measurements derived from SD-OCT did not differ from photographic readings more than the readings of photographs by different readers differed from each other.
Designation of the cup and optic disc boundaries by an automated analysis of SD-OCT was within the range of variable designations by different readers from color stereoscopic photographs, but use of different landmarks typically made the designation of the optic disc size somewhat smaller in the automated analysis. There was better repeatability among measurements from SD-OCT than from among readers of photographs. The repeatability of automated measurement of SD-OCT images is promising for use both in diagnosis and in monitoring of progression.
PMCID: PMC3129482  PMID: 21397334
10.  Comparison of Spectral / Fourier Domain Optical Coherence Tomography Instruments for Assessment of Normal Macular Thickness 
Retina (Philadelphia, Pa.)  2010;30(2):235.
To report normal macular thickness measurements and assess reproducibility of retinal thickness measurements acquired by a time domain optical coherence tomography (OCT)(Stratus [Carl Zeiss Meditec, Inc., Dublin, CA, USA]) and three commercially available spectral / Fourier domain OCT instruments (Cirrus HD-OCT [Carl Zeiss Meditec, Inc., Dublin, CA, USA], RTVue-100 [Optovue, Inc., Fremont, CA, USA], 3D OCT-1000 [Topcon, Inc., Paramus, NJ, USA]).
Forty randomly selected eyes of 40 normal, healthy volunteers were imaged. Subjects were scanned twice during one visit and a subset of 25 was scanned again within 8 weeks. Retinal thickness measurements were automatically generated by OCT software and recorded after manual correction. Regression and Bland-Altman plots were used to compare agreement between instruments. Reproducibility was analyzed by using intraclass correlation coefficients (ICC), and incidence of artifacts was determined.
Macular thickness measurements were found to have high reproducibility across all instruments, with ICC values ranging 84.8–94.9% for Stratus OCT; 92.6–97.3% for Cirrus Cube; 76.4–93.7% for RTVue MM5, 61.1–96.8% for MM6; 93.1–97.9% for 3D OCT-1000 Radial, 31.5–97.5% for 3D Macular scans. Incidence of artifacts was higher in spectral / Fourier domain instruments, ranging 28.75 to 53.16%, compared to 17.46% in Stratus OCT. No significant age or gender trends were found in the measurements.
Commercial spectral / Fourier domain OCT instruments provide higher speed and axial resolution than the Stratus OCT, although they vary greatly in scanning protocols and are currently limited in their analysis functions. Further development of segmentation algorithms and quantitative features are needed to assist clinicians in objective use of these newer instruments to manage diseases.
PMCID: PMC2819609  PMID: 19952997
spectral; Fourier; optical coherence tomography; normal; macular thickness; reproducibility; artifact; segmentation
11.  Comparison of Ultrahigh- and Standard-Resolution Optical Coherence Tomography for Imaging Macular Hole Pathology and Repair 
Ophthalmology  2004;111(11):2033-2043.
To compare ultrahigh-resolution optical coherence tomography (UHR-OCT) technology to a standard-resolution OCT instrument for the imaging of macular hole pathology and repair; to identify situations where UHR-OCT provides additional information on disease morphology, pathogenesis, and management; and to use UHR-OCT as a baseline for improving the interpretation of the standard-resolution images.
Observational and interventional case series.
Twenty-nine eyes of 24 patients clinically diagnosed with macular hole in at least one eye.
A UHR-OCT system has been developed and employed in a tertiary-care ophthalmology clinic. Using a femtosecond laser as the low-coherence light source, this new UHR-OCT system can achieve an unprecedented 3-μm axial resolution for retinal OCT imaging. Comparative imaging was performed with UHR-OCT and standard 10-μm resolution OCT in 29 eyes of 24 patients with various stages of macular holes. Imaging was also performed on a subset of the population before and after macular hole surgery.
Main Outcome Measures
Ultrahigh- and standard-resolution cross-sectional OCT images of macular hole pathologies.
Both UHR-OCT and standard-resolution OCT exhibited comparable performance in differentiating various stages of macular holes. The UHR-OCT provided improved imaging of finer intraretinal structures, such as the external limiting membrane and photoreceptor inner segment (IS) and outer segment (OS), and identification of the anatomy of successful surgical repair. The improved resolution of UHR-OCT enabled imaging of previously unidentified changes in photoreceptor morphology associated with macular hole pathology and postoperative repair. Visualization of the junction between the photoreceptor IS and OS was found to be an important indicator of photoreceptor integrity for both standard-resolution and UHR-OCT images.
Ultrahigh-resolution optical coherence tomography improves the visualization of the macular hole architectural morphology. The increased resolution of UHR-OCT enables the visualization of photoreceptor morphology associated with macular holes. This promises to lead to a better understanding of the pathogenesis of macular holes, the causes of visual loss secondary to macular holes, the timing of surgical repair, and the evaluation of postsurgical outcome. Ultrahigh-resolution optical coherence tomography imaging of macular holes that correspond to known alterations in retinal morphology can be used to interpret retinal morphology in UHR-OCT images. Comparisons of UHR-OCT images with standard-resolution OCT images can establish a baseline for the better interpretation of clinical standard-resolution OCT images. The ability to visualize photoreceptors and their integrity or impairment is an indicator of macular hole progression and surgical outcome.
PMCID: PMC1937401  PMID: 15522369
12.  Retinal Nerve Fiber Layer Thickness Measurement Comparability between Time Domain Optical Coherence Tomography (OCT) and Spectral Domain OCT 
The authors developed an algorithm for measurement comparability between time domain optical coherence tomography (TD-OCT) and spectral domain OCT (SD-OCT). This method may facilitate bridging the gap between measurements obtained by the different generations of OCT technology.
Time domain optical coherence tomography (TD-OCT) has been used commonly in clinical practice, producing a large inventory of circular scan data for retinal nerve fiber layer (RNFL) assessment. Spectral domain (SD)-OCT produces three-dimensional (3-D) data volumes. The purpose of this study was to create a robust technique that makes TD-OCT circular scan RNFL thickness measurements comparable with those from 3-D SD-OCT volumes.
Eleven eyes of 11 healthy subjects and 7 eyes of 7 subjects with glaucoma were enrolled. Each eye was scanned with one centered and eight displaced TD-OCT scanning circles. One 3-D SD-OCT cube scan was obtained at the same visit. The matching location of the TD-OCT scanning circle was automatically detected within the corresponding 3-D SD-OCT scan. Algorithm performance was assessed by estimating the difference between the detected scanning circle location on 3-D SD-OCT volume and the TD-OCT circle location. Global and sectoral RNFL thickness measurement errors between the two devices were also compared.
The difference (95% confidence interval) in scanning circle center locations between TD- and SD-OCT was 2.3 (1.5–3.2) pixels (69.0 [45.0–96.0] μm on the retina) for healthy eyes and 3.1 (2.0–4.1) pixels (93.0 [60.0–123.0] μm on the retina) for glaucomatous eyes. The absolute RNFL thickness measurement difference was significantly smaller with the matched scanning circle.
Scan location matching may bridge the gap in RNFL thickness measurements between TD-OCT circular scan data and 3-D SD-OCT scan data, providing follow-up comparability across the two generations of OCTs.
PMCID: PMC2868471  PMID: 19737886
13.  Diagnostic Ability of Fourier-Domain Versus Time-Domain Optical Coherence Tomography for Glaucoma Detection 
American journal of ophthalmology  2009;148(4):597-605.
To compare retinal nerve fiber layer (RNFL) thickness assessments and the discriminating ability of Fourier-domain optical coherence tomography (FD-OCT) with time-domain optical coherence tomography (TD-OCT) for glaucoma detection.
Prospective, non-randomized, observational cohort study.
Normal and glaucomatous eyes underwent complete examination, standard automated perimetry (SAP), optic disc photography, TD-OCT (Stratus™ OCT, Carl Zeiss Meditec, Dublin, CA) and FD-OCT (RTVue™, Optovue, Inc., Fremont, CA). One eye per subject was enrolled. Two consecutive scans were acquired using a 3.46-mm diameter scan with TD-OCT and a 3.45-mm diameter scan with FD-OCT. For each of 5 RNFL parameters the area under the receiver operator characteristic curve (AUROC) was calculated to compare the ability of FD-OCT and TD-OCT to discriminate between normal and glaucomatous eyes.
Fifty normal (mean age 65.3 ± 9.9 years) and 50 glaucoma patients (mean age 67.7 ± 10.5 years) were enrolled. Average, superior, and inferior RNFL thickness measurements (µm) were significantly (p < 0.01) greater with FD-OCT compared with TD-OCT in normal (103.3 ± 12.6 vs. 96.3 ± 10.7, 134.5 ± 18.6 vs. 113.9 ± 16.3, and 129.7 ± 16.9 vs. 125.5 ±15.8, respectively) and glaucomatous (p < 0.001) eyes (77.6 ± 17.6 vs. 70.4 ± 18.6, 108.0 ± 26.8 vs. 86.8 ± 30.2, 82.2 ± 3.3 vs. 73.5 ± 26.1, respectively). The AUROC for RNFL thickness were similar (p > 0.05) using FD-OCT (average 0.88, superior 0.80, inferior 0.94) and TD-OCT (average 0.87, superior 0.79, inferior 0.95).
Cross-sectional peripapillary RNFL thickness measurements obtained using FD-OCT generated with the RTVue™ are greater than TD-OCT, and have similar diagnostic performance for glaucoma detection.
PMCID: PMC2784699  PMID: 19589493
glaucoma; retinal nerve fiber layer; time-domain OCT; Fourier-domain OCT
14.  Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography 
Ophthalmology  2007;115(5):782-789.e2.
To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT.
Prospective observational case series.
Healthy and glaucomatous subjects in various stages of disease.
Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head.
Main Outcome Measures
Discrimination of retinal tissue layers and detailed visualization of retinal structures.
High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps.
High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma.
PMCID: PMC2846095  PMID: 17884170
15.  Comparison of StratusOCT and Cirrus HD-OCT Imaging in Macular Diseases 
The Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) device is a spectral-domain optical coherence tomography system that allows faster data acquisition than the previous generation StratusOCT (Carl Zeiss Meditec, Dublin, CA), which is a time-domain device. The authors compared images from both units to determine the clinical usefulness of spectral-domain optical coherence tomography technology in patients with macular diseases.
Six consecutive patients were imaged with both the Cirrus HD-OCT and the StratusOCT devices and the images were compared.
Cirrus HD-OCT images were typically more useful than StratusOCT images for assessing fine architectural details in macular pathology. The Cirrus HD-OCT software also facilitated a better understanding of three-dimensional data volumes.
Commercially available spectral-domain optical coherence tomography is a clinically useful tool for visualizing and understanding macular diseases and offers benefits not inherent in previous generation machines.
PMCID: PMC2917043  PMID: 19205492
16.  Noninvasive Volumetric Imaging and Morphometry of the Rodent Retina with High-Speed, Ultrahigh-Resolution Optical Coherence Tomography 
To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models.
A high-speed, ultrahigh-resolution OCT system using spectral, or Fourier domain, detection has been developed for small animal retinal imaging. Imaging is performed with a contact lens and postobjective scanning. An axial image resolution of 2.8 μm is achieved with a spectrally broadband superluminescent diode light source with a bandwidth of ~150 nm at ~900-nm center wavelength. Imaging can be performed at 24,000 axial scans per second, which is ~100 times faster than previous ultrahigh-resolution OCT systems. High-definition and three-dimensional retinal imaging is performed in vivo in mouse and rat models.
High-speed, ultrahigh-resolution OCT enabled high-definition, high transverse pixel density imaging of the murine retina and visualization of all major intraretinal layers. Raster scan protocols enabled three-dimensional volumetric imagingand comprehensive retinal segmentation algorithms allowed measurement of retinal layers. An OCT fundus image, akin to a fundus photograph was generated by axial summation of three-dimensional OCT data, thus enabling precise registration of OCT measurements to retinal fundus features.
High-speed, ultrahigh-resolution OCT enables imaging of retinal architectural morphology in small animal models. OCT fundus images allow precise registration of OCT images and repeated measurements with respect to retinal fundus features. Three-dimensional OCT imaging enables visualization and quantification of retinal structure, which promises to allow repeated, noninvasive measurements to track disease progression, thereby reducing the need for killing the animal for histology. This capability can accelerate basic research studies in rats and mice and their translation into clinical patient care.
PMCID: PMC1941766  PMID: 17122144
17.  Cross-sectional study: Does combining optical coherence tomography measurements using the ‘Random Forest’ decision tree classifier improve the prediction of the presence of perimetric deterioration in glaucoma suspects? 
BMJ Open  2013;3(10):e003114.
To develop a classifier to predict the presence of visual field (VF) deterioration in glaucoma suspects based on optical coherence tomography (OCT) measurements using the machine learning method known as the ‘Random Forest’ algorithm.
Case–control study.
293 eyes of 179 participants with open angle glaucoma (OAG) or suspected OAG.
Spectral domain OCT (Topcon 3D OCT-2000) and perimetry (Humphrey Field Analyser, 24-2 or 30-2 SITA standard) measurements were conducted in all of the participants. VF damage (Ocular Hypertension Treatment Study criteria (2002)) was used as a ‘gold-standard’ to classify glaucomatous eyes. The ‘Random Forest’ method was then used to analyse the relationship between the presence/absence of glaucomatous VF damage and the following variables: age, gender, right or left eye, axial length plus 237 different OCT measurements.
Main outcome measures
The area under the receiver operating characteristic curve (AROC) was then derived using the probability of glaucoma as suggested by the proportion of votes in the Random Forest classifier. For comparison, five AROCs were derived based on: (1) macular retinal nerve fibre layer (m-RNFL) alone; (2) circumpapillary (cp-RNFL) alone; (3) ganglion cell layer and inner plexiform layer (GCL+IPL) alone; (4) rim area alone and (5) a decision tree method using the same variables as the Random Forest algorithm.
The AROC from the combined Random Forest classifier (0.90) was significantly larger than the AROCs based on individual measurements of m-RNFL (0.86), cp-RNFL (0.77), GCL+IPL (0.80), rim area (0.78) and the decision tree method (0.75; p<0.05).
Evaluating OCT measurements using the Random Forest method provides an accurate prediction of the presence of perimetric deterioration in glaucoma suspects.
PMCID: PMC3796272  PMID: 24103806
Optical Coherence Tomography; Visual Field; Random Forest
18.  A joint estimation detection of Glaucoma progression in 3D spectral domain optical coherence tomography optic nerve head images 
Proceedings of SPIE  2014;9035:90350O-.
Glaucoma is an ocular disease characterized by distinctive changes in the optic nerve head (ONH) and visual field. Glaucoma can strike without symptoms and causes blindness if it remains without treatment. Therefore, early disease detection is important so that treatment can be initiated and blindness prevented. In this context, important advances in technology for non-invasive imaging of the eye have been made providing quantitative tools to measure structural changes in ONH topography, an essential element for glaucoma detection and monitoring. 3D spectral domain optical coherence tomography (SD-OCT), an optical imaging technique, has been commonly used to discriminate glaucomatous from healthy subjects. In this paper, we present a new framework for detection of glaucoma progression using 3D SD-OCT images. In contrast to previous works that the retinal nerve fiber layer (RNFL) thickness measurement provided by commercially available spectral-domain optical coherence tomograph, we consider the whole 3D volume for change detection. To integrate a priori knowledge and in particular the spatial voxel dependency in the change detection map, we propose the use of the Markov Random Field to handle a such dependency. To accommodate the presence of false positive detection, the estimated change detection map is then used to classify a 3D SDOCT image into the “non-progressing” and “progressing” glaucoma classes, based on a fuzzy logic classifier. We compared the diagnostic performance of the proposed framework to existing methods of progression detection.
PMCID: PMC4297669  PMID: 25606299
Glaucoma; Markov field; change detection; fuzzy logic classifier
19.  Glaucoma Discrimination of Segmented Cirrus Spectral Domain Optical Coherence Tomography (SD-OCT) Macular Scans 
The British journal of ophthalmology  2012;96(11):1420-1425.
To evaluate the glaucoma discriminating ability of macular retinal layers as measured by spectral-domain optical coherence tomography (SD-OCT).
Healthy, glaucoma suspect and glaucomatous subjects had a comprehensive ocular examination, visual field testing and SD-OCT imaging (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) in the macular and optic nerve head regions. OCT macular scans were segmented into macular nerve fiber layer (mNFL), ganglion cell layer with inner plexiform layer (GCIP), ganglion cell complex (GCC) (composed of mNFL and GCIP), outer retinal complex (ORC) and total retina (TR). Glaucoma discriminating ability was assessed using the area under the receiver operator characteristic curve (AUC) for all macular parameters and mean circumpapillary (cp) RNFL. Glaucoma suspects and glaucoma subjects were grouped together for the calculation of AUCs.
Analysis was performed on 51 healthy, 49 glaucoma suspect and 63 glaucomatous eyes. The median visual field MD was −2.21dB (interquartile range (IQR): −6.92 to −0.35) for the glaucoma group, −0.32dB (IQR: −1.22 to 0.73) for the suspect group and −0.18dB (IQR: −0.92 to 0.71) for the healthy group. Highest age adjusted AUCs for discriminating between healthy and glaucomatous eyes were found for average GCC and GCIP (AUC=0.901 and 0.900, respectively), and their sectoral measurements: infero-temporal (0.922 and 0.913), inferior (0.904 and 0.912) and supero-temporal (0.910 and 0.897). These values were similar to the discriminating ability of the mean cpRNFL (AUC=0.913). Comparison of these AUCs did not yield any statistically significant difference (all p>0.05). Similar discrimination performance but with slight reduction in AUCs was achieved for comparison between healthy and the combination of glaucoma and glaucoma suspect eyes.
SD-OCT GCIP and GCC measurements showed similar glaucoma diagnostic ability and was comparable with that of cpRNFL.
PMCID: PMC3721629  PMID: 22914498
20.  Optical coherence tomography – current and future applications 
Current opinion in ophthalmology  2013;24(3):213-221.
Purpose of review
Optical coherence tomography (OCT) has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high-resolution, cross-sectional images of the retina, retinal nerve fiber layer and the optic nerve head. This review discusses the present applications of the commercially available spectral-domain OCT (SD-OCT) systems in the diagnosis and management of retinal diseases, with particular emphasis on choroidal imaging. Future directions of OCT technology and their potential clinical uses are discussed.
Recent findings
Analysis of the choroidal thickness in healthy eyes and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies has been successfully achieved using SD-OCT devices with software improvements. Future OCT innovations such as longer-wavelength OCT systems including the swept-source technology, along with Doppler OCT and en-face imaging, may improve the detection of subtle microstructural changes in chorioretinal diseases by improving imaging of the choroid.
Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the posterior segment of the eye. Further improvements in both hardware and software technologies should further advance the clinician’s ability to assess and manage chorioretinal diseases.
PMCID: PMC3758124  PMID: 23429598
applications of optical coherence tomography; chorioretinal diseases; retina; spectral-domain optical coherence tomography; swept-source optical coherence tomography
21.  On improving the use of OCT imaging for detecting glaucomatous damage 
The British Journal of Ophthalmology  2014;98(Suppl 2):ii1-ii9.
To describe two approaches for improving the detection of glaucomatous damage seen with optical coherence tomography (OCT).
The two approaches described were: one, a visual analysis of the high-quality OCT circle scans and two, a comparison of local visual field sensitivity loss to local OCT retinal ganglion cell plus inner plexiform (RGC+) and retinal nerve fibre layer (RNFL) thinning. OCT images were obtained from glaucoma patients and suspects using a spectral domain OCT machine and commercially available scanning protocols. A high-quality peripapillary circle scan (average of 50), a three-dimensional (3D) scan of the optic disc, and a 3D scan of the macula were obtained. RGC+ and RNFL thickness and probability plots were generated from the 3D scans.
A close visual analysis of a high-quality circle scan can help avoid both false positive and false negative errors. Similarly, to avoid these errors, the location of abnormal visual field points should be compared to regions of abnormal RGC+ and RNFL thickness.
To improve the sensitivity and specificity of OCT imaging, high-quality images should be visually scrutinised and topographical information from visual fields and OCT scans combined.
PMCID: PMC4208344  PMID: 24934219
Glaucoma; Imaging; Optic Nerve; Psychophysics
22.  Comparison of Retinal Nerve Fiber Layer Thickness Measurement Bias and Imprecision across Three Spectral-Domain Optical Coherence Tomography Devices 
We compared retinal nerve fiber layer (RNFL) bias and imprecision among three spectral-domain optical coherence tomographs (SD-OCT).
A total of 152 eyes of 83 subjects (96 healthy and 56 glaucomatous eyes) underwent peripapillary RNFL imaging using at least 2 of the following 3 SD-OCT devices on the same day: Cirrus HD-OCT (optic nerve head [ONH]) cube 200 × 200 protocol), RTVue-100 (ONH protocol [12 radial lines and 13 concentric circles]), and 3D OCT-1000 (3D Scan 256 × 256 protocol). Calibration equations, bias and imprecision of RNFL measurements were calculated using structural equation models.
The calibration equations for healthy and glaucoma RNFL thickness measurements among the 3 devices were: Cirrus = 2.136 + 0.831*RTVue; Cirrus = −15.521 + 1.056*3D OCT-1000; RTVue = −21.257 + 1.271*3D OCT-1000. Using Cirrus bias as an arbitrary reference, RTVue bias was 1.20 (95% CI 1.09–1.32, P < 0.05) times larger and 3D OCT-1000 was 0.95 (0.87–1.03, P > 0.05) times smaller. Relative to 3D OCT-1000, the RTVue bias was 1.27 (1.13–1.42, P < 0.05). RTVue imprecision (healthy eyes 7.83, 95% CI 6.43–9.58; glaucoma cases 5.71, 4.19–7.64) was statistically significantly higher than both Cirrus (healthy eyes 3.23, 2.11–4.31; glaucoma cases 3.53, 0.69–5.24) and 3D OCT-1000 (healthy eyes 4.07, 3.11–5.35; glaucoma cases 5.33, 3.77–7.67) in healthy eyes. The imprecision also was significantly higher for RTVue measurements in healthy compared to glaucomatous eyes. None of the other comparisons was statistically significant.
RTVue-100 showed higher imprecision (or higher measurement variability) than Cirrus HD-OCT and 3D OCT-1000 RNFL measurements. Three-dimensional cube scanning with post-hoc data sampling may be a factor reducing imprecision.
RTVue-100 showed worse imprecision (higher measurement variability) than Cirrus HD-OCT and 3D OCT-1000 retinal nerve fiber layer measurements. The results might be related to the use of raster scanning by the later devices, while RTVue uses a combination of radial and concentric scanning pattern.
PMCID: PMC3390182  PMID: 22538423
23.  A Formula to Predict Spectral Domain Optical Coherence Tomography (OCT) Retinal Nerve Fiber Layer Measurements Based on Time Domain OCT Measurements 
To establish and validate a formula to predict spectral domain (SD)-optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness from time domain (TD)-OCT RNFL measurements and other factors.
SD-OCT and TD-OCT scans were obtained on the same day from healthy participants and patients with glaucoma. Univariate and multivariate linear regression relationships were analyzed to convert average Stratus TD-OCT measurements to average Cirrus SD-OCT measurements. Additional baseline characteristics included age, sex, intraocular pressure, central corneal thickness, spherical equivalent, anterior chamber depth, optic disc area, visual field (VF) mean deviation, and pattern standard deviation. The formula was generated using a training set of 220 patients and then evaluated on a validation dataset of 105 patients.
The training set included 71 healthy participants and 149 patients with glaucoma. The validation set included 27 healthy participants and 78 patients with glaucoma. Univariate analysis determined that TD-OCT RNFL thickness, age, optic disc area, VF mean deviation, and pattern standard deviation were significantly associated with SD-OCT RNFL thickness. Multivariate regression analysis using available variables yielded the following equation: SD-OCT RNFL = 0.746 × TD-OCT RNFL + 17.104 (determination coefficient [R2] = 0.879). In the validation sample, the multiple regression model explained 85.6% of the variance in the SD-OCT RNFL thickness.
The proposed formula based on TD-OCT RNFL thickness may be useful in predicting SD-OCT RNFL thickness. Other factors associated with SD-OCT RNFL thickness, such as age, disc area, and mean deviation, did not contribute to the accuracy of the final equation.
PMCID: PMC3464321  PMID: 23060724
Glaucoma; Retinal nerve fiber layer; Spectral domain optical coherence tomography; Time domain optical coherence tomography
24.  High-speed Ultrahigh Resolution Optical Coherence Tomography before and after Ranibizumab for Age-related Macular Degeneration 
Ophthalmology  2009;116(5):956-963.
To evaluate intraretinal anatomy in patients with exudative age-related macular degeneration (AMD) using high-speed ultrahigh resolution optical coherence tomography (hsUHR-OCT) before and 1 month after intravitreal injection of ranibizumab.
Retrospective case series.
Twelve eyes of 12 patients.
A broad bandwidth superluminescent diode laser light source and spectral/Fourier domain signal detection were used to create a prototype hsUHR-OCT instrument with 3.5 μm axial image resolution and approximately 25,000 lines/second acquisition speed. Twelve eyes of 12 patients with exudative AMD were imaged with hsUHR-OCT before and 1 month after intravitreal ranibizumab injection. High pixel density and raster-scanned 3-dimensional (3D) OCT data sets were generated. Three-dimensional imaging software was used to calculate subretinal/retinal pigment epithelium fluid volume and volume of the fibrovascular lesion.
Main Outcome Measures
Qualitative and quantitative analysis of hsUHR-OCT images and 3D data sets.
All eyes had some degree of normalization of macular contour after intravitreal ranibizumab. The inner/outer photoreceptor segment junction visualized on hsUHR-OCT was discontinuous, overlying the fibrovascular lesion in all 12 of 12 eyes both before and after treatment; 9 of 12 eyes had focal areas of thinning of the outer nuclear layer, which remained after treatment. Volumetric measurements were possible in 8 of 12 eyes with 3D-rendering software. Fibrovascular lesion volume did not change significantly after treatment.
hsUHR-OCT is capable of unprecedented imaging speed and resolution, making it a valuable instrument in measuring in vivo intraretinal pathology. All 12 eyes had some normalization of macular contour. Fibrovascular lesion volume did not change significantly 1 month after treatment, suggesting that ranibizumab does not cause much initial regression of preexisting neovascular tissue. Photoreceptor abnormalities remained in all patients after treatment of wet AMD, suggesting that although ranibizumab improves overall retinal architecture, some photoreceptor damage may be irreversible.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references.
PMCID: PMC2846085  PMID: 19410953
25.  Integration and fusion of standard automated perimetry and optical coherence tomography data for improved automated glaucoma diagnostics 
BMC Ophthalmology  2011;11:20.
The performance of glaucoma diagnostic systems could be conceivably improved by the integration of functional and structural test measurements that provide relevant and complementary information for reaching a diagnosis. The purpose of this study was to investigate the performance of data fusion methods and techniques for simple combination of Standard Automated Perimetry (SAP) and Optical Coherence Tomography (OCT) data for the diagnosis of glaucoma using Artificial Neural Networks (ANNs).
Humphrey 24-2 SITA standard SAP and StratusOCT tests were prospectively collected from a randomly selected population of 125 healthy persons and 135 patients with glaucomatous optic nerve heads and used as input for the ANNs. We tested commercially available standard parameters as well as novel ones (fused OCT and SAP data) that exploit the spatial relationship between visual field areas and sectors of the OCT peripapillary scan circle. We evaluated the performance of these SAP and OCT derived parameters both separately and in combination.
The diagnostic accuracy from a combination of fused SAP and OCT data (95.39%) was higher than that of the best conventional parameters of either instrument, i.e. SAP Glaucoma Hemifield Test (p < 0.001) and OCT Retinal Nerve Fiber Layer Thickness ≥ 1 quadrant (p = 0.031). Fused OCT and combined fused OCT and SAP data provided similar Area under the Receiver Operating Characteristic Curve (AROC) values of 0.978 that were significantly larger (p = 0.047) compared to ANNs using SAP parameters alone (AROC = 0.945). On the other hand, ANNs based on the OCT parameters (AROC = 0.970) did not perform significantly worse than the ANNs based on the fused or combined forms of input data. The use of fused input increased the number of tests that were correctly classified by both SAP and OCT based ANNs.
Compared to the use of SAP parameters, input from the combination of fused OCT and SAP parameters, and from fused OCT data, significantly increased the performance of ANNs. Integrating parameters by including a priori relevant information through data fusion may improve ANN classification accuracy compared to currently available methods.
PMCID: PMC3167760  PMID: 21816080

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