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Editors Selection IGR 15-2

Imaging Techniques: Spectral-domain OCT and ganglion cell complex thickness

Comment by David Garway-Heath on:

24997 Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography, Tan O; Chopra V; Lu AT et al., Ophthalmology, 2009; 116: 2305-2314

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The role of clinical imaging devices is to aid diagnosis and identifying progression in patients with, or at risk of, glaucoma. High measurement repeatability is needed if a parameter is to be useful to identify progression. Tan et al. (1501) evaluated the diagnostic precision and repeatability of new parameters derived from the ganglion cell complex (GCC) thickness, measured in macular images of a spectral-domain OCT. They reported that the diagnostic precision of GCC parameters was similar, and complementary, to peripapillary retinal nerve fibre layer (RNFL) thickness (as measured by time-domain OCT) and the measurement repeatability was better than for RNFL thickness.

Glaucoma is a chronic progressive optic neuropathy characterised by loss of retinal ganglion cells (RGCs) and their axons. At least one third of RGCs lie in posterior pole, so there is a clear rationale for attempting to quantify the RGC volume in the macula. Furthermore, the ratio of visual field test points to number of RGCs is much lower in the central retina compared to more peripheral retina. The implication is that macular imaging and RGC quantification may be more sensitive than VF testing if early glaucomatous defects in this region are discrete and lie between VF test locations.

Macular imaging and RGC quantification may be more sensitive than VF testing if early glaucomatous defects in this region are discrete and lie between VF test locations

The diagnostic precision of GCC thickness in this study was equivalent to time-domain OCT RNFL thickness measurements. However, the cut-off values of a number of GCC parameters were derived from the study 'normal group' and tested in the 'perimetric glaucoma group', whereas only RNFL thickness and macula thickness were evaluated from time-domain OCT. The greater the number of parameters derived from a dataset, when those parameters are tested in the same dataset, the greater is the chance of finding a parameter that outperforms a conventional measurements (such as time-domain RNFL thickness). Validation in another dataset is required.

Several of the GCC parameters were designed to identify focal damage. It would be interesting to see whether similar statistical approaches applied to RNFL thickness measurements might improve the diagnostic precision of the RNFL further.

The actual level of diagnostic precision may also be over-stated because the authors required their normal subjects to have 'a normal appearing optic nerve head [and] a normal NFL'. Thus the normal group may represent a 'super-normal' population. Similarly, the 'perimetric glaucoma group' were required to have clear structural damage, thus potentially over-estimating the sensitivity of the GCC and RNFL parameters to identify glaucomatous nerves in this population.

With the methods applied, the diagnostic precision of GCC parameters was similar to RNFL thickness, but the identified patients were not identical (9% of perimetric glaucoma patients had GCC parameters outside the normal range, despite having a RNFL within the normal range), leading the authors to suggest that the GCC measurements are complementary to RNFL thickness measurements. This conclusion should be viewed with an element of caution, because this additional 9% was identified if any of three GCC parameters were outside the normal range. The specificity (false positive rate) of this approach was not reported, but is likely to be higher than 5%. Furthermore, variability in measurements may also contribute to an apparent dissociation between two diagnostic parameters.

Concordant patterns of GCC and RNFL loss will greatly improve a clinician's confidence of glaucomatous damage in the context of equivocal or unreliable visual fields

The reported repeatability for GCC parameters was encouraging and suggests that they may be suitable for monitoring patients for progression. The repeatability is a measure of the precision of measurements taken at the same sitting and by the same technician. To evaluate the clinical utility of GCC measurements for progression detection, we also need to know the reproducibility of measurements (measurements taken on another day and/or by another technician). Repeatability and reproducibility are usually correlated, so one may expect GCC measurements to be reproducible, but this needs to be demonstrated.

Although some caveats to the authors' conclusions have been described, there are clear potential benefits to RGC quantification and giving clinicians access to RGC parameters is exciting. The finding of concordant patterns of GCC and RNFL loss will greatly improve a clinician's confidence of glaucomatous damage in the context of equivocal or unreliable visual fields.

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