Advances in correlating RGC loss and perimetric changes

Cambridge, England-Assessing glaucoma used to be simple when clinicians combined the evaluations of the optic disc and the visual field to assess the health of the optic nerve. With advances in technology, there are now a number of ways to assess the topography of the optic nerve head, the nerve fiber layer (NFL), and the retinal ganglion cell (RGC) complex. Keith Martin, MD, FRCOphth, discussed “a growing issue in glaucoma” about how these data can be used to determine accurately the underlying biology of glaucoma, i.e., the relationship between RGC loss and visual field (VF) loss.

Dr. Martin, professor of ophthalmology, University of Cambridge, Cambridge, England, presented four key points in the correlation of RGC loss and perimetric changes.

First, RGC loss in glaucoma is associated with a variety of structural changes that can be measured and that are correlated with perimetric changes.

Previous studies have suggested that from 25% to 35% of RGC loss is associated with VF loss. However, the RGC count is highly variable, and even in normal individuals the RGC cell count can vary by a factor of 2.

“Low RGC density is not the same as RGC loss,” he said.

Longitudinal studies in animals may shed more light on the relationship between RGC loss and perimetry, something that post-mortem human studies cannot do. Studies of induced glaucoma in monkeys have suggested that the RGC density often decreased before functional loss is detected. However, VF loss exceeding 5 dB can occur at normal RGC density, which re-emphasizes that RGC density is not the same as RGC loss, according to Dr. Martin, and the functional consequences of the two may differ.

Combining retinal imaging using spectral-domain optical coherence tomography (SD-OCT) measurements of the NFL with perimetry provides “a very good correlation between the VF performance and the SD-OCT estimates of RGC loss. Regarding combining these measures, this looks very promising,” he said.

Second, different structural measures do not always vary together. Investigators need to be wary about considering data from different instruments together. For example, injecting colchicine intravitreally causes a decrease in the retinal NFL on scanning laser polarimetry but not on OCT.

Third, structural measures of RGC pathology could be very useful in the future. Dr. Martin suggested the value of having tests that can assess damage in RGC cells in vivo before cell death. Ultra-high resolution OCT may allow subcellular changes to be detected that are correlated with neuronal health or possibly neuronal activity.

“The ability to detect sick RGCs when rescue is still possible would be extremely attractive,” he commented.

And fourth, combined structure-function indices are evolving rapidly and are likely to be widely used in the future. In the laboratory, axonal transport can now be imaged in real time. He said he believes that it will not be long before functional measures can be seen using imaging.

This article is based on Dr. Martin’s presentation during Glaucoma Subspecialty Day at the 2012 American Academy of Ophthalmology annual meeting.

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