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Editors Selection IGR 15-4

Progression: Structure-function relationship

Comment by Chris Leung on:

51118 The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change, Medeiros FA; Zangwill LM; Bowd C et al., Investigative Ophthalmology and Visual Science, 2012; 53: 6939-6946

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Assessment of structural and functional changes of the optic nerve is fundamental to diagnose and monitor glaucoma. Although there are many options in the clinic to measure the optic nerve head and the visual field, direct counting and functional assessment of individual retinal ganglion cells (RGCs) is not yet possible. With reference to the empirical formulas derived by Harwerth et al.^1,2, Medeiros and colleagues estimated RGC counts of 397 normal, suspect and glaucomatous eyes based on their standard automated perimetry and OCT RNFL measurements, and examined the structure function relationship in glaucoma. They showed that for the same degree of RGC loss, the corresponding changes in MD and RNFL thickness varied with the stages of the disease, with more reduction in RNFL thickness in the early stages and more reduction in MD in the late stages. In following early glaucoma patients, substantive neural loss could be missed if progression analysis is solely based on linear regression analysis between MD and time. This study provides an insightful interpretation of the structure function relationship in glaucoma and lays the foundation to integrate structural and functional data for assessment of glaucomatous damage. Estimating RGC count from clinical data is not easy. There are assumptions in the empirical formulas which may not be met. For example, the estimation of RGC count from SAP data assumes the RGC density to be uniform over a retinal area corresponding to an area of visual field that separates test locations. In the estimation of RGC count from OCT RNFL data, the formulas incorporate visual field MD to account for the association between neuronal and nonneuronal components of OCT RNFL thickness. The inclusion of a functional index may add variance to the RGC estimates and bias the comparison of MD and RNFL thickness with RGC counts. As shown in Figure 3A (relationship between average RNFL thickness and RGC counts), the range of RGC counts for a given average RNFL thickness is wide.

Another issue that needs to be addressed is the translation from visual field loss in MD to functional disability. Although the drop in MD is less in the early stages than that in the advanced stages for the same degree of neural loss, the corresponding impact of functional impairment may also be less. The ongoing investigation of performance-based tests of visual impairment in glaucoma by the authors is highly relevant.

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