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Editors Selection IGR 17-1
Basic Science: Neuronal Function in Experimental Glaucoma
Comment by Koen Vermeer on:
60996 Relating Retinal Ganglion Cell Function and Retinal Nerve Fiber Layer (RNFL) Retardance to Progressive Loss of RNFL Thickness and Optic Nerve Axons in Experimental Glaucoma, Fortune B; Cull G; Reynaud J et al., Investigative Ophthalmology and Visual Science, 2015; 56: 3936-3944
The nature of the relation between retinal function and structure is a topic that is notoriously difficult to study in a clinical setting. Despite impressive improvements in imaging technology in recent years, clinically used measures such as thickness and retardance of the RNFL are still surrogate markers for actual loss of axons.
Fortune et al. studied changes in function and structure in experimental glaucoma (EG) in 39 nonhuman primates (NHPs). They considered RNFL thickness (by SD-OCT) and retardance (by scanning laser polarimetry; SLP) as in-vivo structural parameters, mfERG as in-vivo functional parameters and complete postmortem optic nerve axon counts as ex-vivo structural parameters.
Analysis of the in-vivo data by linear regression showed that retardance was significantly affected before a change in RNFL thickness was measured.
Retardance was significantly affected before a change in RNFL thickness was measured
Similar results were found for the mfERG high-frequency component (HFC) amplitude. These results indicate that both structural and functional changes occur before loss of RNFL tissue can be demonstrated by thickness measurements.
Relative axon counts (ratio of axon counts in the EG eye over the control eye) were obtained in 31 NHPs. Linear regression with RNFL thickness showed no significant offset, suggesting that RNFL thickness loss was a good surrogate for loss of axons in these eyes. Linear regression with the other parameters again showed significant loss of RNFL retardance and mfERG HFC amplitude before differences in optic nerve axon counts could be demonstrated.
Structural and functional changes occur before loss of RNFL tissue can be demonstrated by thickness measurements
In conclusion, loss of both retinal ganglion cell function and RNFL retardance was demonstrated in this study before loss of RNFL thickness and optic nerve axons. This suggests that clinical care could benefit from considering changes within the RNFL itself, such as retardance (measured by SLP or polarization-sensitive OCT1) or OCT-derived attenuation coefficients.2 While these results obtained in EG in NHPs may not be directly transferable to the natural history of glaucoma in human eyes, they provide a great foundation for the design of new clinical studies addressing structure-function relationships.
References
- Pircher M, Hitzenberger CK, Schmidt-Erfurth U. Polarization sensitive optical coherence tomography in the human eye. Prog Retin Eye Res 2011;30(6):431-451.
- Vermeer KA, van der Schoot J, Lemij HG, de Boer JF. RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment. Invest Ophthalmol Vis Sci 2012;53(10):6102-6108.
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