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Rodent models of intraocular pressure (IOP)-induced optic neuropathy are providing important clues on how retinal ganglion cell (RGC) axons are injured at the level of the optic nerve head. Technological advances now allow imaging of the rat and mouse optic nerve head with the potential of performing serial imaging to track changes over time. Guo et al. (911) describe a modification of optical coherence tomography (OCT) whereby serial transverse (en face) sections are obtained to derive various parameters to describe the optic disc. They compare this method (eOCT) to confocal scanning laser ophthalmoscopy (CSLO) using the older, and now obsolete, Zeiss device in a group of rats with experimentally elevated IOP according to the model developed by Morrison et al.
The authors performed several analyses comparing eOCT to CSLO and firmly contend that eOCT is a superior technique. The Heidelberg Retina Tomograph (HRT) has been modified for use in rat and the changes induced by elevated IOP in rat been described. Unfortunately with their CSLO technique, Guo et al. do not provide any indices of topographic changes which are readily available with the HRT, and therefore the appropriate conclusion is that eOCT may be superior to the CSLO system used by them, but not necessarily to all systems available. This is an important point as the HRT has undergone significant software and hardware modifications that make it a much improved device.
A potential advantage of eOCT is to track changes in anterior and posterior scleral canal opening (ASCO and PSCO respectively), a potentially important parameter in experimental IOP induced damage as proposed by Burgoyne and others. However, it is possible that delineating the disc margin with CSLO may provide an adequate estimate of the ASCO and it is a pity that the authors did not show the correlation between optic disc area and ASCO. The authors state that the hypothesis that cupping in rat (as measured by the HRT) is a late indicator of RGC loss may be incorrect because of the insensitivity of the HRT. They further postulate that eOCT is a more sensitive technique. It is unfortunate the authors provide no RGC survival data in their study to support their assertion. It is interesting to note that Guo et al. show a mean increase in disc area of over 20,000 µm2 in their animals. The diameter of the rat optic disc is approximately 200 µm (hence an area of around 63,000 µm2). The increase in disc area of over 30% and dramatic increase in ASCO shown in the example in the paper are impressive changes. These changes were previously observed in animals with very significant axonal loss. Therefore a corollary of the hypothesis that eOCT is a sensitive technique is that these animals sustained very high degrees of axonal loss causing structural changes that were readily detectable.
Cupping may be a late feature of RGC loss in this model since there are fundamental differences in the optic disc architecture between rat and primate. Rats have little if any physiological cupping and the retinal vessels provide substantial support to the disc surface; hence cupping may not be evident until the IOP is very high. Since rats have a virtually absent lamina cribrosa, the nature of cupping rats and primates is likely very different.
New imaging techniques have a great potential in the evaluation of experimental models of optic neuropathy. eOCT is one of these techniques and further quantitative research with a logical comparison with the HRT is warranted to demonstrate its merit.