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Editors Selection IGR 15-1

Clinical Examination Methods: Morphological changes and Visual Field Progression

Comment by Brad Fortune on:

72739 Impact of Rates of Change of Lamina Cribrosa and Optic Nerve Head Surface Depths on Visual Field Progression in Glaucoma, Wu Z; Lin C; Crowther M et al., Investigative Ophthalmology and Visual Science, 2017; 58: 1825-1833

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The promise of using OCT to image deeper optic nerve head (ONH) structures such as the lamina cribrosa in order to detect change and predict future glaucoma progression becomes increasingly clear with results of meaningful studies such as the one by Wu and colleagues. This study used OCT scans to measure two ONH parameters: the anterior lamina cribrosa surface depth (ALSCD) and ONH surface depth (ONHSD), each relative to two different internal reference planes: one defined by the pair of Bruch's Membrane Opening (BMO) points in each OCT B-scan, the other defined by the choroid-sclera interface (CSI) detected just adjacent to the ONH. The latter is arguably more stable with regard to fluctuations of choroidal thickness, which have been shown to influence the axial position of the BMO plane. Wu and colleagues used trend analysis to determine rates of change for these 4 OCT parameters of ONH structure in a large cohort of glaucoma patients and used elegant statistical modeling to determine if those rates had any influence on the likelihood of visual field progression (as determined by EMGT criteria for standard automated perimetry). The investigators found that:

"The risk of development of VF progression increased by 6.4% (BMO-based measurements) to 7.4% (CSI-based measurements) for each micrometer per year increase in the rate of change of ALCSD, and by 10.9% (BMO-based measurements) and 9.3% (CSI-based measurements) for each micrometer per year increase in the rate of change of ONHSD after controlling for the covariates." And they concluded ultimately that this: "finding underscores the importance of monitoring the ALCSD and ONHSD for risk assessment of VF progression in glaucoma patients."

This study reports compelling evidence that the anterior lamina cribrosa surface and the optic nerve head surface measured by OCT provide biomarkers capable of predicting subsequent visual field progression in glaucoma

In their Discussion section, the authors also consider other important findings from their study such as that older age was associated with a slower rate of change of ALCSD and ONHSD (i.e., less rapid increase in the depth of either surface, confirming similar observations previously predicted and published by others) but also that higher IOP during follow-up was associated with a faster rate of change of both parameters (i.e., a more rapid increase in the depth of either surface). The authors rely on their complete set of findings to synthesize the reasonable suggestion that lowering IOP (particularly in those eyes exhibiting a rapid increase of ALCSD and ONHSD) should reduce the rate of change as well as the risk of subsequent visual field progression.

The strengths of the study by Wu and colleagues include that it was based on a large cohort (146 eyes of 95 glaucoma patients) and long duration of regular, frequent (every 4 months) follow-up scans; to quote: "The mean follow-up duration was 6.5 years (range, 5.0-7.4 years) and the mean number of follow-up visits for each patient was 17.3 (range, 8-21 visits)." Further, the investigators applied elegant statistical models to control for baseline variables including baseline age, baseline axial length, baseline central corneal thickness, baseline ALCSD/ONHSD and IOP during follow-up. It is also reassuring that they found positive results despite using an ONH scan pattern that consisted of only 6 radial B-scans. Their measurements to derive the ONH parameters ALCSD and ONHSD were generally very careful, for example, using a spatially weighted average to adjust for sampling density inherent to a radial scan pattern.

However, in this regard, there are also a few caveats to consider for future studies of this kind. First, the investigators performed their measurement in B-scan images scaled as 1:1 pixel (i.e., "square pixels"), then applied the instrument's estimates for pixel size to report (and presumably analyze) depth measurements of the ALC and ONH surfaces relative to each reference plane. These depth measurements were made perpendicular to the reference plane, but the orientation of that plane would change once the correct scaling is applied to the images (i.e. if the images were scaled 1:1 µm instead of 1:1 pixel) for all cases in which the reference plane was not perfectly parallel to the image frame. This means the "normal" to the reference plane would also have a different orientation and thus intersect the surface of interest (such as the lamina cribrosa) at a different point, which could lead to errors especially in eyes with highly curved surfaces.

Another related limitation is that all measurements were two dimensional (made within each B-scan) rather than three-dimensional. It is not likely that the results of the study would change with these improvements, more precise measurements, but it is worth the endeavor for future studies. Another question arises about results not reported in this fine paper. Figure 2 showed Venn Diagrams to document the agreement between the two different parameters (ONHSD and ALCSD) for each reference plane, which was generally quite good, reassuring. But it also would be important to know whether there was also good agreement between the two different reference planes (within each parameter). That is because if the choroid thins and causes the BMO to move posteriorly - but not the ONH tissue/surface - then the parameter ONHSD would decrease relative to the BMO but not the CSI reference plane; similarly, the ALCSD would not change for CSI but would decrease for BMO reference plane. In any case, it was reassuring to see at least good agreement for the two different parameters when the same reference plane was used for each. In summary, this study reports compelling evidence that the anterior lamina cribrosa surface and the optic nerve head surface measured by OCT provide biomarkers capable of predicting subsequent visual field progression in glaucoma.

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