Hood DC, Kardon RH .A framework for comparing structural and functional measures of glaucomatous damage

Department of Psychology, Columbia University, 116th and Broadway, New York, NY, 10027-7004, USA.
Progress in Retinal and Eye Research (Impact Factor: 8.73). 12/2007; 26(6):688-710. DOI: 10.1016/j.preteyeres.2007.08.001
Source: PubMed


While it is often said that structural damage due to glaucoma precedes functional damage, it is not always clear what this statement means. This review has two purposes: first, to show that a simple linear relationship describes the data relating a particular functional test (standard automated perimetry (SAP)) to a particular structural test (optical coherence tomography (OCT)); and, second, to propose a general framework for relating structural and functional damage, and for evaluating if one precedes the other. The specific functional and structural tests employed are described in Section 2. To compare SAP sensitivity loss to loss of the retinal nerve fiber layer (RNFL) requires a map that relates local field regions to local regions of the optic disc as described in Section 3. When RNFL thickness in the superior and inferior arcuate sectors of the disc are plotted against SAP sensitivity loss (dB units) in the corresponding arcuate regions of the visual field, RNFL thickness becomes asymptotic for sensitivity losses greater than about 10dB. These data are well described by a simple linear model presented in Section 4. The model assumes that the RNFL thickness measured with OCT has two components. One component is the axons of the retinal ganglion cells and the other, the residual, is everything else (e.g. glial cells, blood vessels). The axon portion is assumed to decrease in a linear fashion with losses in SAP sensitivity (in linear units); the residual portion is assumed to remain constant. Based upon severe SAP losses in anterior ischemic optic neuropathy (AION), the residual RNFL thickness in the arcuate regions is, on average, about one-third of the premorbid (normal) thickness of that region. The model also predicts that, to a first approximation, SAP sensitivity in control subjects does not depend upon RNFL thickness. The data (Section 6) are, in general, consistent with this prediction showing a very weak correlation between RNFL thickness and SAP sensitivity. In Section 7, the model is used to estimate the proportion of patients showing statistical abnormalities (worse than the 5th percentile) on the OCT RNFL test before they show abnormalities on the 24-2 SAP field test. Ignoring measurement error, the patients with a relatively thick RNFL, when healthy, will be more likely to show significant SAP sensitivity loss before statistically significant OCT RNFL loss, while the reverse will be true for those who start with an average or a relatively thin RNFL when healthy. Thus, it is important to understand the implications of the wide variation in RNFL thickness among control subjects. Section 8 describes two of the factors contributing to this variation, variations in the position of blood vessels and variations in the mapping of field regions to disc sectors. Finally, in Sections 7 and 9, the findings are related to the general debate in the literature about the relationship between structural and functional glaucomatous damage and a framework is proposed for understanding what is meant by the question, 'Does structural damage precede functional damage in glaucoma?' An emphasis is placed upon the need to distinguish between "statistical" and "relational" meanings of this question.

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Available from: Randy H Kardon, Mar 11, 2014
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    • "Standard automated perimetry (SAP) has traditionally been used as the gold standard for evaluation of progressive damage in glaucoma [4]. However, several large prospective clinical studies have shown that many patients can present progressive structural optic nerve or retinal nerve fiber layer (RNFL) damage without detectable losses on SAP [5] [6] [7] [8]. In many patients, progressive structural damage frequently precedes functional deterioration, giving clinicians an opportunity to start or intensify treatment before the disease causes significant functional deterioration [9]. "
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    ABSTRACT: Detection of progression and measurement of rates of change is at the core of glaucoma management, and the use of Spectral Domain Optical Coherence Tomography (SD-OCT) has significantly improved our ability to evaluate change in the disease. In this review, we critically assess the existing literature on the use of SD-OCT for detecting glaucoma progression and estimating rates of change. We discuss aspects related to the reproducibility of measurements, their accuracy to detect longitudinal change over time, and the effect of aging on the ability to detect progression. In addition, we discuss recent studies evaluating the use of combined structure and function approaches to improve detection of glaucoma progression.
    The Open Ophthalmology Journal 05/2015; 9(1):78-88. DOI:10.2174/1874364101509010078
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    • "Glaucoma is a progressive optic neuropathy characterized by structural changes of the optic nerve and retina that are associated with visual functional defects [1]. However, as Hood and Kardon [1] mentioned, there is no consensus regarding the relationship between the functional loss of sensitivity to light and the structural loss of retinal ganglion cell axons. "
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    ABSTRACT: Purpose To evaluate the relationship between the structural damage as assessed by time-domain optical coherence tomography (OCT) and functional changes in glaucoma. Methods In total, 190 patients with normal tension glaucoma or primary open angle glaucoma were included in this study. The thickness of retinal nerve fiber layer (RNFL) around the optic disc and the area of RNFL defect were determined using OCT scans. The relationships between the RNFL thickness or area of the defect and visual field (VF) indices were assessed using the Lowess function, regression analysis and partial Spearman correlation. The differences between these associations depending on the stage of VF damage were further analyzed. Age, optic disc size, refraction, central corneal thickness and the presence of systemic disease were corrected for in order to exclude confounding factors. Results A logarithmic scale of RNFL thickness showed a negative linear relationship with VF indices. The area of the RNFL defect showed a weak correlation with the pattern of standard deviation, whereas the remnant RNFL thickness was moderately correlated with the pattern of standard deviation (partial Spearman correlation coefficient, 0.39, -0.47, respectively; p < 0.0001). Many outliers were detected in the Lowess-plotted graphs. Multiplication of the area and the inverted RNFL thickness showed a moderately correlated logarithmic relationship with the VF indices (partial Spearman correlation coefficient, 0.46; 95% confidence interval, 0.34 to 0.57; p < 0.0001). In the severe stage of VF damage, correlation between the area of the RNFL defect and mean deviation was significantly greater than in other stages (partial Spearman correlation coefficient, -0.66; p = 0.02). Conclusions The thickness of the RNFL had a negative logarithmic correlation with the VF indices and was more relevant to the VF indices than the area of the RNFL defect, as measured by OCT.
    Korean Journal of Ophthalmology 08/2014; 28(4):323-9. DOI:10.3341/kjo.2014.28.4.323
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    • "Atrophy of the ganglion cell layer (GCL) is a reliable predictor for poor visual function [13] and correlates at the topographic level with the visual fields (VF) deficits. In cases of glaucoma [14] and chiasm tumours [15], atrophy of the GCL has been shown to correlate with permanent visual field imapirment. "
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    ABSTRACT: Objective Retrograde trans-synaptic degeneration of retinal ganglion cell layer (GCL) has been proposed as one of the mechanisms contributing to permanent disability after visual pathway damage. We set out to test this mechanism taking advantage of the new methods for imaging the macula with high resolution by optical coherence tomography (OCT) in patients with lesions in the posterior visual pathway. Additionally, we explored the association between thinning of GCL as an imaging marker of visual impairment such as visual field defects. Methods Retrospective case note review of patients with retrogeniculate lesions studied by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the visual fields. Results We analysed 8 patients with either hemianopia or quadrantanopia due to brain lesions (stroke = 5; surgery = 2; infection = 1). We found significant thinning of the GCL in the projecting sector of the retina mapping to the brain lesion. Second, we found strong correlation between the PD of the visual field quadrant and the corresponding macular GCL sector for the right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001). Conclusions The mapping between lesions in the posterior visual pathway and their projection in the macula GCL sector corroborates retrograde trans-synaptic neuronal degeneration after brain injury as a mechanism of damage with functional consequences. This finding supports the use of GCL thickness as an imaging marker of trans-synaptic degeneration in the visual pathway after brain lesions.
    PLoS ONE 05/2014; 9(5):e97444. DOI:10.1371/journal.pone.0097444 · 3.23 Impact Factor
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