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Section Heading Glaucoma sub Section Glaucoma Diagnosis and Monitoring Using Advanced Imaging Technologies Mitra Sehi, PhD 1 and Shawn M Iverson, DO 2 1. Research Assistant Professor of Ophthalmology; 2. Glaucoma Research Fellow, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Palm Beach Gardens, Florida Abstract Advanced ocular imaging technologies facilitate objective and reproducible quantification of change in glaucoma but at the same time impose new challenges on scientists and clinicians for separating true structural change from imaging noise. This review examines time-domain and spectral-domain optical coherence tomography, confocal scanning laser ophthalmoscopy and scanning laser polarimetry technologies and discusses the diagnostic accuracy and the ability of each technique for evaluation of glaucomatous progression. A broad review of the current literature reveals that objective assessment of retinal nerve fiber layer, ganglion cell complex and optic nerve head topography may improve glaucoma monitoring when used as a complementary tool in conjunction with the clinical judgment of an expert. Keywords Confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography, Fourier-domain optical coherence tomography, scanning laser polarimetry (SLP), retinal nerve fiber layer, optic nerve head, glaucoma progression Disclosure: The authors have no conflicts of interest to declare. Received: November 10, 2012 Accepted: January 5, 2013 Citation: US Ophthalmic Review, 2013;6(1):15–25 Correspondence: Mitra Sehi, PhD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 7101 Fairway Drive, Palm Beach Gardens, FL 33418, USA. E: msehi@med.miami.edu Role of Imaging in Glaucoma Glaucoma results from accelerated loss of retinal ganglion cells (RGCs) and their axons, leading to retinal nerve fiber layer (RNFL) attenuation and optic neuropathy. 1,2 Glaucomatous damage is characterized by specific pattern of damage to the optic nerve head (ONH) and visual field loss. 3,4 Established methods for detecting these changes include clinical examination of the ONH and RNFL, optic disc stereophotography, and fundus photography. 5,6 Glaucoma progresses slowly and it is important to detect real change due to disease that is beyond normal age loss and short-term and long-term fluctuations. Advanced ophthalmic imaging devices provide objective quantitative measures of neuroretinal rim, RNFL thickness and ONH topography with high repeatability and low variability. 7,8 One of the challenging aspects of ocular imaging is improving signal-to-noise ratio, 9–13 and detecting real structural change due to disease that is beyond the normal variability. 14–25 Different imaging technologies use different algorithms for this purpose. Several reports have indicated that these technologies are capable of identifying glaucomatous damage at an early stage. 26–36 A recent comprehensive review by the Ophthalmic Technology Assessment Committee Glaucoma Panel of the American Academy of Ophthalmology concluded that information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant clinical parameters. 37 Several imaging technologies have included progression analysis packages that compile several visit dates into trend based analysis designed to assist the clinician in monitoring glaucoma progression. 38–43 In order for progression analysis to be useful in clinical practice, three criteria must be met: © To u ch MEd ica l MEdia 2013 the measurements must be reproducible and have minimal noise, follow-up images must be accurately registered to each other, and a statistical test must distinguish between true biological change and instrument measurement variability. Preliminary studies for optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (CSLO) and scanning laser polarimetry (SLP) have shown these methods are capable of detecting change in glaucomatous eyes or eyes of glaucoma suspects over time. 39–41,44–46 Confocal Scanning Laser Ophthalmoscopy Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Germany) is a CSLO that uses a single diode laser with a wavelength of 670 nm. An automatic pre-scan with a depth of 4–6 mm determines the correct location of the focal plane, the required scan depth and the level of sensitivity needed to capture high quality images. 47 Using the Scanning Tomography technique, three sets of three-dimensional images are acquired. The field of view is 15° x 15° and each acquisition comprises 384x384 pixels. Sixteen images per millimeter of scan depth are acquired. If the quality of images in at least one of the series is not good enough (for reasons such as fixation loss), the acquisition is automatically continued until three useful series are obtained. For each location, several reflected light intensities are measured at different focal planes in different depth locations. The distribution of these light intensities along the optical axis ‘z’ (confocal z-profile) has a symmetrical shape with the highest intensity at the location of the light-reflecting surface. When this calculation is performed at all locations in the section image planes, the result is a matrix of 384x384 15