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Editors Selection IGR 15-2

Structure Tests and Anatomy: Progression analysis by OCT

Comment by George Lambrou on:

25152 Evaluation of retinal nerve fiber layer progression in glaucoma: a study on optical coherence tomography guided progression analysis, Leung CK; Cheung CY; Weinreb RN et al., Investigative Ophthalmology and Visual Science, 2010; 51: 217-222

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What is glaucoma progression and how do you detect it before it is too late? This question has been central to the management of glaucoma for decades, together with another important debate: is it function or structure that should be in the forefront of our concerns, knowing that the two are poorly correlated at certain stages of the disease? With the coming of age of computer-based perimetry in the nineties, the issue seemed resolved: it became possible to quantify visual field defects reliably and algorithms were developed to detect progression, conceived essentially as increasing loss-of-function. This paradigm, however, may be about to change: We are witnessing today a similar coming of age of computerbased anatomical examination techniques. The development of algorithms to quantify progression in terms of lossof- structure is the expected next step. The paper by Leung et al. (221) describes such an approach using Stratus OCT performed on 116 eyes of 64 patients, each having had at least four RNFL examinations over a period of three to five years. The authors have calculated a straightforward measure of RNFL loss, the Guided Progression Analysis (GPA), which is simply the rate of RNFL thickness change (slope of regression line of thickness over time) expressed in µm/ year.

The new generation of RNFL imaging technologies provides a yet-untapped wealth of information on the structural changes occurring at retinal level

For each eye they calculated three GPAs: the average GPA (based on RNFL measurements across all meridians), the any-clockhour GPA (based on measurements in twelve clock-hour sectors) and the two-adjacent-clock-hour GPA (based on analyzing pairs of neighboring clock-hour sector RNFLs ‐ an approach reminiscent of the cluster analysis of visual field points in perimetry). At the same time they estimated functional progression using the rate of change of the Visual Field Index (VFI) from SITA standard 24-2 perimetry performed at the same time as the RNFL examinations.

As the disease progresses, functional performance becomes dependant on an ever-more compromised structure

Not unexpectedly, any-clock-hour GPA identified the highest number of patients (56 eyes, 48% of the total) as having progressed. The other two approaches ( average GPA and two-clock-hour GPA) identified much lower and roughly identical numbers of 'progressors' (21 and 22 eyes respectively, 18-19% of total), from which, however, only 14 eyes were identified by both GPAs: the rest was detected by one but not the other of the two methods. Interestingly, the VFI trend analysis identified a similar number of progressors (22 eyes, 19% of total), but here the overlap with average-GPA progressors was minimal. Only three eyes showed both structural and functional progression, while 37 eyes, equally distributed, showed either the one or the other.

Minimal incremental structural deterioration has significant functional consequences

What are then the take-home messages of this study? Firstly, that the new generation of RNFL imaging technologies provides a yetuntapped wealth of information on the structural changes occurring at retinal level in glaucoma. Secondly, that the structure-function discrepancy is moving to front stage again, but this time we are better prepared to understand it: as the authors of the paper hint, the curvilinear ‐ possibly logarithmic ‐ nature of this relationship implies that in early stages of the disease significant structural damage is occurring with limited, if any, functional impact. Then, as the disease progresses, functional performance becomes dependant on an evermore compromised structure, so that minimal incremental structural deterioration has significant functional consequences, accounting for the asymmetry in the glaucoma continuum. Finally, that quantitative estimation of loss-of-structure progression is here to stay, although it will take further long-term studies to develop parameters permitting a reliable prediction of disease prognosis and evaluation of treatment response for the better management of our patients.

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