While clinical examination of the optic disc remains essential to glaucoma diagnosis and management, it is a complex process and difficult to adequately document specific findings in a permanent record.1,2 Even when drawings or notations are documented in a patient’s record, two-dimensional conceptual representations, such as the cup-to-disc ratio, are limited when applied to this complex three-dimensional structure. For example, the edge of the optic “cup” is commonly sloped such that its dimensions vary with the longitudinal position (axial depth) of the measurement plane. It is difficult to identify an axial plane precisely under conditions of live examination (such as binocular indirect ophthalmoscopy) or even within stereoscopic photographs.
Therefore, it is not surprising that even highly trained specialists do not agree with each other, or repeat with high precision, judgments about the degree of glaucomatous structural damage or the likelihood of its progression when viewing stereoscopic color photographs of the optic disc.3-8 So, while most experts are likely to agree on an initial diagnosis, it remains difficult to detect subtle changes in optic disc structure on the basis of clinical examination with or without stereo photos — hence the intense interest over the past two decades in the ongoing development of imaging techniques capable of providing objective, quantitative, reliable measurements of optic disc structure.9
With these proven capabilities, objective imaging techniques have become an integral component of both clinical examination and research in glaucoma.10
CSLT – AN EARLY TECHNIQUE
Among these techniques, confocal scanning laser tomography (CSLT) effectively paved the way. The Heidelberg Retina Tomograph (HRT) ultimately grew to become the most thoroughly implemented and widely adopted platform for performing CSLT and has been incorporated into clinical practice and glaucoma research, including as an ancillary outcome measure for randomized clinical trials.11-16
CSLT provides a high-resolution, two-dimensional map of optic disc surface topography by detecting the strong reflection produced at the interface between the vitreous and the optic disc or retinal tissue. Once an axial reference plane and the optic disc margin are defined, the cup can be defined as that portion inside the disc where its surface lies posterior to the reference plane. Similarly, the neuroretinal rim tissue can be measured with relatively high precision as the area inside the disc that lies anterior to (or “above”) the reference plane.
However, this approach has three potential drawbacks that can affect repeatability and accuracy. First, the disc margin is user defined (subjective) and based on tissue reflectance properties that do not necessarily correspond consistently to specific anatomical structures (i.e., the anatomy defining the disc margin can vary between eyes or even between radial sectors of the same eye).17,18 Second, the rim width measurements are made parallel to the axial reference plane, which does not reflect the geometric orientation of the nerve fibers passing through the rim in the vast majority of eyes.19,20 Third, variability of the axial reference plane ultimately hampers both the precision and accuracy of CSLT measurements and the ability to detect structural changes in glaucoma.21-23
The latter constraint is akin to the problem facing clinicians during live examination and/or evaluation of stereo photos: It is difficult to establish a reliable axial reference plane. Given this inherent limitation common to both approaches, there is only modest agreement between CSLT and expert analysis of stereo photos for detecting progressive structural changes of the optic disc.13,24,25
OCT – TECHNOLOGICAL ADVANTAGES
In this context, one of the fundamental advantages of optical coherence tomography (OCT) is its capability of producing cross-sectional images through tissue with high axial resolution. This allows for the identification of specific anatomical structures deeper within the optic nerve head (ONH) with high precision and accuracy. These capabilities should ultimately solve the previously mentioned reference plane and disc margin problems by enabling those definitions to be based on direct visualization of specific anatomic entities, such as the Bruch’s membrane opening (BMO), the anterior scleral surface or perhaps the anterior scleral canal opening.26-28
Most OCT instruments used in a clinical setting already include fixed scan protocols for glaucoma diagnosis and management, as well as software to report parameters of optic disc neuroretinal rim thickness, rim area, rim volume and, similarly, cup area or volume. OCT measurements of these structural markers already implemented in commercial OCT software packages generally perform well in clinical research studies and enhance diagnostic capability beyond isolated use of stereoscopic disc photos or other OCT parameters.29-33
OCT – LATEST RESEARCH FINDINGS
This remains a very active field of research that continues to develop and produce results that can influence clinical care and commercial instrumentation. Two focal points have shown early promise in clinical research studies.
The first focal point is the ability to visualize and measure aspects of lamina cribrosa anatomy in-depth using OCT.34-38 It has long been thought that the lamina cribrosa is the primary site of injury to retinal ganglion cell axons in glaucoma. OCT provides the ability to measure its depth, thickness, curvature and other aspects of its shape as well as microscopic aspects of lamina cribrosa anatomy such as beam thickness, pore size, pore density and pore shape. This should offer future insights into pathophysiology and the ability to refine estimates of risk for a given eye — that is, to help determine if an eye is relatively more or less susceptible to develop glaucoma or rapidly progressing disease. OCT imaging of the lamina cribrosa for glaucoma assessment is still on the horizon for clinical implementation and thus beyond the scope of this article, but there are excellent recent reviews on this topic.39-41
The second focal point of recent research has been the development of new standards for other OCT-based measurements of optic disc structure as they pertain to glaucoma diagnosis. Perhaps most immediate among them is an approach to measuring neuroretinal rim thickness based on minimum distance mapping. As introduced by Povazay et al42 and subsequently shown by Chen to have meaningful clinical utility,43 ONH rim tissue thickness measurements derived via minimum distance determination have several important advantages. First and foremost is the geometrical relationship to the orientation of axon bundles as they pass through the rim area to enter the scleral canal and exit the globe. The minimum distance approach constrains the thickness measurement to being made at the thinnest point along the rim and as close to being perpendicular to the axon bundles as possible.17,18
This theoretical strength has meaningful clinical benefits, such as avoiding overestimates of rim thickness produced by methods based on less sound geometry. This results in improved diagnostic performance44 and stronger correlations to visual field sensitivity.20,45,46
When ONH rim tissue thickness is measured in an OCT scan as the distance from the BMO point to the nearest point along the optic disc surface, it is commonly termed the BMO-minimum rim width (BMO-MRW, or simply MRW) (Figure 1A, page 27).17,18 The MRW parameter enhances diagnostic performance compared to methods of rim width measurement based on less appropriate geometry, such as implemented in CSLT or older OCT approaches, where the width is determined “horizontally” (within the reference plane) and from an outer edge defined by the clinical disc margin instead of by the BMO.44,46
However, optic discs with a larger diameter have a thinner neuroretinal rim for the same number and caliber of axons. Therefore, to have the best possible diagnostic utility, measurements of rim width (i.e. rim thickness) need to be adjusted for disc size.47,48 Alternatively, the total cross-sectional area of rim tissue should be directly proportional to the total number and caliber of axons in each eye and thus unrelated to disc size. Hence the same approach for minimum distance mapping has also been applied to measure the optic disc rim area.45 Gardiner, et al demonstrated that the minimum rim area (MRA) parameter (Figure 1B) exhibited stronger correlation to visual field sensitivity and to peripapillary retinal nerve fiber layer (RNFL) thickness than the HRT- or OCT-derived “horizontal” measurements of rim area.45 Although, the MRW parameter (rim width) correlated equally well to the visual field and RNFL thickness in that study even without adjustment for disc size.45,48 It is likely that disc size has greater impact at the extremes for very small or very large discs or discs of highly myopic eyes.46,49,50 Other similar approaches based on minimum distance mapping have confirmed the advantages it provides for glaucoma diagnostics.51-53
Some of the earliest work in this area was conducted in experimental glaucoma models, which showed that the disc rim tissue thinned earlier and to a greater degree than the peripapillary RNFL tissue.47,54-56 Thus, applying OCT measures of the optic disc rim tissue to glaucoma diagnosis in a cross-sectional, population-based manner may provide additional benefit. However, other work has shown that measurement variability is somewhat larger for MRW and MRA compared with peripapillary RNFL thickness.57 This may be one reason that the correlation with orbital optic nerve axon counts over a wide range of glaucomatous damage is stronger for peripapillary RNFL thickness than for either of these two parameters of the neuroretinal rim.58
Future work in this area will include methods for global optimization of the minimum distance defining rim thickness42,59 rather than the localized method currently employed, although recent work suggests that this will provide only marginal (if any) additional improvement.59 Also, the effect of normal aging on rim parameters such as MRW and MRA will be important to consider and incorporate into commercial instrument reports.60
The ability of OCT to provide high-resolution, cross-sectional images through the optic disc tissue enables improved visualization, as well as accurate and precise measurement of anatomical structures important to glaucoma diagnostics and pathophysiology. Important structural targets for OCT include the neuroretinal rim tissue, the BMO, the anterior scleral canal opening and various aspects of lamina cribrosa morphology.
Combined with emerging standards for clinical OCT scan acquisition protocols and morphometric measurements based on the minimum distance approach, these new diagnostic parameters such as MRW and MRA offer meaningful benefits to glaucoma diagnosis and detection of progression. For example, it is likely that in some cases optic disc rim thinning will occur prior to thinning of the RNFL or macular ganglion cell layer, which means OCT measurements like MRW or MRA could enhance early detection of glaucoma. These OCT-based neural rim measurements may also help differentiate glaucoma from other optic neuropathies (which generally exhibit less deformation and “cupping”).
Nevertheless, other structural imaging targets, such as thickness of the peripapillary RNFL and macular inner retinal layers, remain important to detection and management of glaucoma, not least because of their high test–retest repeatability, so they should continue to be used in conjunction with OCT scans of the ONH for maximum efficacy. Ideally, instrument makers will include results of all three target areas in standard glaucoma reports going forward. OM
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