|Year : 2019 | Volume
| Issue : 2 | Page : 21-26
Optical coherence tomography in glaucoma
Chandan Govind Tiple
Department of Ophthalmology, G.M.C., Chandrapur, Maharashtra, India
|Date of Submission||11-Feb-2016|
|Date of Acceptance||15-Aug-2020|
|Date of Web Publication||27-Nov-2020|
Dr. Chandan Govind Tiple
S/O G.N. Tiple, Ashok Nagar, Near Ashok Buddha Vihar, Visapur, Tah-Ballarpur, Chandrapur - 442 701, Maharashtra
Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. Spectral-domain OCT allows for unprecedented simultaneous ultrahigh-speed, ultrahigh-resolution ophthalmic imaging. The higher resolution, currently at 5–7 μm commercially, can provide images of subtle abnormalities or progression currently not visible with time-domain-OCT and would potentially allow improved segmentation and greater accuracy in measurements of retinal layers. A review of the evidence to date suggests that the retinal nerve fiber layer remains the dominant parameter for early diagnosis of glaucoma and the detection of its progression.
Keywords: Glaucoma diagnosis and progression, optical coherence tomography, retinal nerve fiber layer
|How to cite this article:|
Tiple CG. Optical coherence tomography in glaucoma. Albasar Int J Ophthalmol 2019;6:21-6
| Introduction|| |
Glaucoma is a multi-factorial optic neuropathy characterized by progressive structural loss of retinal ganglion cells (RGC) that may result in vision loss and irreversible blindness. The ability to detect structural loss is fundamental in the diagnosis and management of glaucoma. While glaucomatous structural damage can be assessed subjectively by clinically examining the optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL), the introduction of ocular imaging modalities into clinical management has allowed for supplemental objective and quantitative evaluation of ocular structure.
Optical coherence tomography (OCT) is a new optical device that permits a noncontact, noninvasive, high-resolution, and cross-sectional tomographic imaging of the posterior segment of the eye as well as quantitative assessment of different layers. Compared to current diagnostic techniques, OCT is not limited by ocular aperture, does not lack sensitivity nor reproducibility, and still achieves a high axial resolution of approximately 5 μm.
Given how pervasive OCT is in the clinical practice of ophthalmology, it is sobering to realize that the development of ophthalmic OCT began just under 20 years ago. The first retinal imaging was performed in 1989 by Huang et al. in Massachusetts. The first prototype ophthalmic OCT was placed at the New England Eye Center in Boston, Massachusetts, and in vivo, ocular imaging of subjects began in 1994. In 1994, the patented technology was transferred to Carl Zeiss Meditec, Inc. (Dublin, California, USA). The first commercially available OCT, called OCT 1000, was marketed in 1996. The technology went through 2 iterations, resulting in OCT 2000 in the year 2000 and then OCT3 (stratus OCT) in 2002. In 2006, the first high speed, high-resolution OCTs, known variously as Fourier domain OCT, spectral domain (SD)-OCT or high-speed high resolution-OCT (all describing the same technology), became commercially available.
The first demonstration of OCT was presented by Huang and colleagues in Science in 1991 to image a human retina and coronary artery ex vivo., Fercher and associates presented the firstin vivo OCT images in 1993 and Schuman et al., produced the first images of retinal disease (Axial resolution 10 μm) in 1995. A major event in the evolution of OCT was the use of light wavelengths instead of time delay to determine the spatial location of reflected light. Through the use of Fourier transformation, this took the technology from the original method of time-domain (TD)-OCT to the development of SD-OCT; which enables much faster acquisition times, resulting in a large increase in the amount of data that can be obtained during a given scan duration using SD-OCT.,,
The SD-OCT was the first described by Wojtkowskl et al. in 2001. The first SD-OCT ophthalmic scans were presented in 2002, where in vivo scans of the iris, lens, macula, and optic disc were all displayed. From this early experimental start, SD-OCT devices have been approved for clinical use by the US Food and Drug Administration and can now acquire 3D data sets consisting of several hundred scan of 200 × 200 × 1024 pixels in 2 s. The history of the OCT technology demonstrates the rapid expansion of the field of OCT, with new research appearing continuously.
Current image analysis technology requires additional development in order to take advantage of the powerful potential of SD-OCT imaging. At present, we are limited to total retinal thickness and RNFL segmentation on many SD-OCT devices.
Three-dimensional SD-OCT imaging is currently under research, improve reproducibility, sensitivity, and specificity in the detection of disease and its progression; These 3-D OCT data cubes can be registered to allow measurement of exactly the same tissue areas subsequently, reducing measurement variability and enhancing sensitivity and specificity. Adaptive optics combined with OCT can allow for 3D imaging of cellular structures such as cone photoreceptors, microvasculature, and RNFL bundles. SD-OCT also has the potential to gather retinal functional data that could be associated with glaucoma. For example, Doppler OCT to visualize and measure retinal blood flow, and specific frequencies from the spectral data can provide information about blood oxygenation in retinal vessels. Optophysiology for functional glaucoma assessment, by measurements of changes in reflectance of retinal tissue, when exposed to light. Thus, as the technology matures, SD-OCT may be used to provide heretofore difficult-to-realize or even unobtainable clinically relevant information beyond retinal structure.
| Optical Coherence Tomography in Glaucoma|| |
OCT is of particular utility in glaucoma since it provides high resolution, objective, quantitative assessment of the retinal cellular layers affected by the disease. Especially as glaucoma is a disease currently defined by clinical appearance of the optic nerve and visual field and as RNFL precedes visual field loss by 6 years.,, RNFL thinning may, in theory, be the earliest structural change clinically detectable. RNFL imaging, therefore, maybe the best way to diagnose preperimetric glaucoma.
Past OCT research in glaucoma has primarily focused on TD-OCT. SD OCT allows for unprecedented simultaneous ultrahigh-speed, ultrahigh-resolution ophthalmic imaging. The higher resolution, currently at 5–7 μm commercially, can provide images of subtle abnormalities or progression currently not visible with TD-OCT and would potentially allow improved segmentation and greater accuracy in measurements of retinal layers.,
SD OCT technology can image the classic structural changes like thinning of the RNFL, as well as the loss of the normal high RNFL reflectivity in glaucomatous eyes. It can also image changes in blood vessels associated with RNFL thinning. Second-order blood vessels, which are completely buried within the thick healthy RNFL in the normal eye, become exposed and are seen above the retinal surface as the surrounding RNFL thins in the glaucomatous eye.
SD-OCT is able to demonstrate a statistically significant improvement in the reproducibility in peripapillary RNFL thickness measurements over the clinical standard for TD-OCT, more so, for sectoral measurement than global measurements. Thus making it especially useful to detect focal tissue loss seen in the earlier stages of glaucoma. The quality of reporting of diagnostic studies for glaucoma using OCT has been demonstrated overall to be suboptimal, with only 26.7% of selected papers reporting more than half of the standards for the reporting of diagnostic accuracy studies criteria items.
There is a reported difference in RNFL thickness measurement between different SD-OCT devices attributed to variation in optical properties and segmentation algorithms, and therefore the measurements are not inter-changeable between devices. However, despite these variations, the devices have demonstrated similar diagnostic capabilities.
Pieroth et al. analyzed glaucomatous eyes with known focal defects of the nerve fiber layer (RNFL), relating OCT findings to clinical examination, RNFL and stereoscopic ONH photography, and Humphrey 24-2 visual fields. In most eyes with focal RNFL defects, OCT showed significant thinning of the RNFL in areas closely corresponding to focal defects visible on clinical examination, to red-free photographs, and to defects on the Humphrey visual fields. OCT enabled the detection of focal defects in the RNFL with a sensitivity of 65% and a specificity of 81%, revealing that RNFL thickness in eyes with focal defects showed good structural and functional correlation with clinical parameters.
Pieroth et al. found a specificity of 81% and a sensitivity of 65% of detecting focal defects solely through statistical analysis of OCT measurements (i.e., without clinical interpretation of the tomographic OCT scan).
Hoh et al. evaluated the relationship between visual function and RNFL measurements obtained with scanning laser polarimetry (SLP) and OCT in 17 normal, 23 ocular hypertensives, and 38 glaucomatous eyes. Eyes with glaucoma had mean RNFL thickness measured with OCT compared with normal and ocular hypertensive eyes, respectively (all P < 0.005). All SLP parameters were significantly associated with OCT-generated RNFL thickness. OCT and SLP were capable of differentiating glaucomatous from nonglaucomatous populations in this cohort; however, considerable measurement overlap was observed among normal, ocular hypertensive, and glaucomatous eyes. RNFL structural measurements demonstrated a good correlation with visual function.
Bowd et al. analyzed OCT data from 61 normal eyes (from patients aged 23–80 years). Their study revealed a significant correlation between age and RNFL thickness in the temporal quadrant (r = −0.32, P = 0.01) and a trend a significant correlation between age and RNFL thickness in the superior quadrant. Correlations were weak between age and RNFL thickness in the nasal and inferior quadrants.
Bowd et al. compared the thickness of the RNFL in ocular hypertensive eyes (n = 28) with age-matched normal (n = 30) and glaucomatous eyes (n = 29) using the OCT (OCT 2000), they found that mean RNFL was significantly thinner in ocular hypertensive eyes (72.8 μm) than in normal eyes (85.8 μm). Specifically, in the inferior quadrant, 84.4 μm versus 107.6 μm and in the nasal quadrant, 44.1 μm versus 61.8 μm. RNFL was significantly thinner in glaucomatous eyes than in ocular hypertensive and normal eyes throughout 360° and in all quadrants, suggesting that quantitative differences in RNFL thickness exist between age-matched ocular hypertensive, normal and glaucomatous eyes.
Mok et al. revealed a significant negative correlation between age and RNFL thickness in normal subjects as measured by OCT, which correlated well with histopathological findings.
Kanamori et al. evaluated the relationship between visual field and RNFL thickness measured by OCT and the ability of OCT to distinguish between early glaucomatous or glaucoma-suspect eyes from normal eyes. They found a significant relationship between the mean deviation (MD) and RNFL thickness in all parameter, excluding the 3-0'clock area. Of in all parameters, the average RNFL thickness had the strongest correlation (r = −0.729, P < 0.001). Suggesting that the measurement of RNFL thickness by OCT is useful in detecting early RNFL damage and in monitoring glaucomatous changes.
Guedes et al. reported that the inferior RNFL was the only parameter in which a statistically significant difference was observed between normals and glaucoma suspect group.
Sony et al. quantified the normative values for peripapillary RNFL thickness with OCT 3 in 146 normal Indian subjects. The average RNFL thickness in the sample population under study was 104.27 μm. The RNFL was thickest in the inferior quadrant, followed by the superior quadrant, and progressively less in nasal and temporal quadrant. The difference between inferior and superior quadrants was not statistically significant. Age had a significant negative correlation with average RNFL thickness (r = −0.321, P = 0.000), superior (r = −0.233, P = 0.005), and inferior RNFL thickness (r = −0.234, P = 0.004).
Medeiros et al. compared the ability of stratus OCT, GDx-VCC (SLP) and HRT II (Confocal Scanning Laser Ophthalmoscopy The HRT II (software version 3.0, Heidelberg Engineering, Dossenheim, Germany) was used to acquire CSLO images) to discriminate between normal and glaucomatous eyes. They found that the largest areas under the receiver operating characteristic (ROC) curve was for stratus OCT and that OCT-specifically, inferior RNFL thickness and GDx (nerve fiber indicator) performed significantly better than HRT.
Sihota et al. compared the ONH parameters using OCT in normals, primary open-angle glaucoma (POAG) and chronic primary angle-closure glaucoma (CPACG) patients. They found a significant difference in disc area (P < 0.01), cup area (P < 0.01), rim area (P < 0.01), vertical integrated rim area (P < 0.01), rim volume (P < 0.01) and cup/disc ratio (P < 0.01) in normal versus POAG versus CPACG eyes respectively. Thus, concluding that OCT may serve as a useful diagnostic modality in distinguishing a normal optic disc from an early glaucomatous one (both early POAG and CPACG).
Ramakrishnan et al. obtained the normative values for peripapillary RNFL thickness with OCT 3 in 118 normal Indian subjects. The mean ± standard deviation RNFL thickness for various quadrants of superior, inferior, nasal, temporal, and average were 138.2 ± 21.74, 129.1 ± 25.67, 85.71 ± 21, 66.38 ± 17.37, and 104.8 ± 38.81 μm, respectively. There was no significant difference in the measurements between males and females, and no significant correlation with respect to age.
Subbiah et al. correlated the finding of OCT evaluation of RNFL thickness with visual field changes in 30 glaucomatous, 30 ocular hypertensive and 30 normal eyes and found that the mean RNFL thickness was significantly less in ocular hypertensive (P = 0.008) and glaucomatous eyes (P < 0.001), than in normal. Ocular hypertensive had thinner RNFL in the nasal, inferior, and temporal quadrants (P < 0.001) when compared to normals. Global indices in ocular hypertensive on short-wave automated perimetry did not correlate significantly with the RNFL thickness, concluding that OCT is capable of detecting RNFL changes in ocular hypertensive eyes.
Badala et al. studied the diagnostic performance of qualitative evaluation of stereoscopic optic disc photographs and contemporary versions of three quantitative imaging techniques-OCT, SLP (GDx-VCC) and CSLO (HRT III) in patients with early to moderate perimetric glaucoma and concluded that each imaging technique independently performed as well as, but not better than, evaluation of stereo-photographs by experienced clinicians. Main obstacle being, the subjectivity and variability of clinical assessment of optic disc photos. Among the quantitative techniques, Stratus OCT was more sensitive for detection of glaucoma at high specificity (95%) than HRT III.
Badala et al. found stratus OCT to have the largest areas under the ROC curve and the greatest sensitivities at 80% and at 95% specificities for average RNFL thickness and the thickness in the inferior quadrant to have the largest areas under the ROC curve and the greatest sensitivities at 80% and at 95% specificities. Sensitivity likely would improve when more normative data are available.
Hood et al. estimated that the sensitivity and specificity of OCT RNFL thickness was 95% and 98%, respectively.
Chen were the first to study the ability of SD OCT to qualitatively and quantitatively evaluate ONH and RNFL glaucomatous structural changes and correlate quantitative SD-OCT parameters with disc photography and visual fields in eyes with varying stages of open-angle glaucoma (i.e., early, moderate, late) and normal eyes. They found classic glaucomatous ONH and RNFL structural changes in SD-OCT images which showed good correlation with disc photography and visual field testing. In their study, they stressed that best age-matched normal controls are important, because the RNFL normally thins with aging. Hence, controls were age-matched.
Taliantzis et al. correlated the functional changes in visual fields with OCT findings in patients with ocular hypertension (n = 54), open-angle glaucoma (n = 73) and suspected glaucoma (n = 42). A moderate correlation between RNFL thickness and indices mean sensitivity 0.547, mean defect (MD)-0.582 and loss variance of VF-0.527, (P < 0.001) was observed for all patients. Correlations of ocular hypertension and preperimetric groups are weak. Correlation of RNFL thickness with global indices becomes stronger as the structural alternations become deeper in the OCT examination. Correlation of RNFL thickness with the global index of VF in respective segments around optic disc was also calculated and was significant in the nasal, inferior, superior and temporal segments. Concluding that segmental RNFL and not RNFL average thickness is a reliable index for early diagnosis of glaucoma and for the follow-up of patients with ocular hypertension. The mean defect (MD) index of VF seems to be more sensitive for the follow-up of patients with ocular hypertension.
Once glaucoma is diagnosed, a sensitive method for the detection of progression is essential because appropriately intensifying treatment can slow RGC loss and preserve vision. The detection of glaucoma progression with OCT remains a challenge because when assessing structural changes over time, it is difficult to discriminate between glaucomatous structural damage and measurement variability or age-related structural loss.
Wollstein et al. showed the potential use of OCT in detecting glaucomatous progression with an event-based approach (i.e., a change greater than the expected variability was considered progression). Using a prototype, they concluded that the OCT was more sensitive than standard visual fields for the detection of progression. In fact, 22% of eyes had a significant change measured by the OCT without corresponding deterioration of the visual fields. However, it was not clear whether these eyes were true progressors undetected by visual fields or false positives due to the variability of the measurements or age-related thinning of the RNFL.
Mwanza et al. studied intra-visit and inter-visit measurements of peripapillary RNFL thickness and ONH parameters with Cirrus SD-OCT showing excellent reproducibility, indicating that this instrument may be useful in monitoring glaucoma progression. When comparing two measurements from the same eye on two different visits, a reproducible decrease in average RNFL thickness of approximately 4 μm or more may be considered a statistically significant change from baseline.
Wessel et al. showed the significant difference in the rate of structural change between glaucoma progressors (2.12 μm/year) and nonprogressors (−1.18 μm/year).
Naghizadeh et al. (2014) studied that Glaucoma eyes had nonsignificant rates of structural change in RNFL (−0.33 μm/year), cup area (0.03 mm 2/year), rim area (−0.03 mm 2/year) and ganglion cell complex (GCC) (−0.19 μm/year). Only GCC global (3.8%/year) and focal (1.5%/year) loss volumes had significant rates of structural change compared with healthy eyes.
In Na et al. study, there was no significant difference in sensitivity to detect glaucoma progression among RNFL (5%), total macular thickness (14%), and ganglion cell inner plexiform layer (8%).
Sung et al. studied that glaucoma progressors had structural rates of RNFL change of −1.19 μm/year and macular thickness −4.74 μm/year. By visual field index, glaucoma progressors had structural rates of RNFL change of −2.08 μm/year and macular thickness −5.12 μm/year. Only macular rates of change were significantly different from glaucoma nonprogressors.
Na et al. showed Glaucoma progressors had significantly different rates of structural change in RNFL (−1.26 μm/year), rim area (−0.02 mm 2/year), average cup to disc ratio (0.004/year) and macular cube volume (−0.07 μm/year) compared with glaucoma nonprogressors.
These studies indicate that the macular region is appropriate for the detection of glaucoma progression; however, they are all limited by short follow-up periods that did not last more than 2 years.
In summary, the literature to date suggests that SD-OCT detects RNFL thinning before the development of the visual field or optic neuropathy, especially in the inferior and temporal quadrant. Segmental RNFL thickness, particularly in the inferior quadrant, seems to be a more reliable index for the early diagnosis of glaucoma. RNFL thickness is a dominant parameter in the detection of glaucoma progression. However, macular parameters might provide a useful alternative for glaucoma progression assessment.
| Conclusions|| |
SD-OCT is a valuable clinical tool for early diagnosis of glaucoma and detection of its progression. RNFL parameters have been demonstrated to provide accurate information for disease diagnosis and sensitive method for disease progression.
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Conflicts of interest
There are no conflicts of interest.
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