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Editors Selection IGR 15-4
Experimental Glaucoma: Where's the primary site of nerve fiber damage?
Comment by Chris Leung on:
55319 Does optic nerve head surface topography change prior to loss of retinal nerve fiber layer thickness: a test of the site of injury hypothesis in experimental glaucoma, Fortune B; Reynaud J; Wang L et al., PLoS ONE, 2013; 8: e77831
Progressive optic nerve head (ONH) deformation and retinal nerve fiber layer (RNFL) thinning are two fundamental processes in glaucoma but less is known about whether ONH deformation is a cause or a consequence of RNFL thinning. Fortune and colleagues set out to investigate the longitudinal changes of the ONH surface topology and RNFL imaged by confocal scanning laser ophthalmoscopy (CSLO) and optical coherence tomography (OCT), respectively, in 68 Rhesus monkeys induced with experimental glaucoma, and tested the hypothesis that ONH changes can be detected prior to observable RNFL thinning. They elevated the intraocular pressure (IOP) by applying laser photocoagulation onto the trabecular meshwork and showed that at the onset of significant ONH surface height change, 25% of eyes had significant reduction of average RNFL thickness whereas at the onset of significant RNFL thickness change, 71% had significant reduction of the ONH surface height. This result corroborates their earlier finding demonstrating that RNFL did not show significant thinning on average until 15 days after the onset of ONH surface topology change in experimental glaucoma (Fortune B, et al., Invest Ophthalmol Vis Sci 2012;53:3939-3950). With a similar study design, Strouthidis and colleagues also reported no significant change in RNFL thickness at the onset of CSLO detected ONH surface depression (Invest Ophthalmol Vis Sci 2011;52:1206-1219). These studies lay out an important foundation for investigating the sequence of ONH and RNFL changes in glaucoma. However, it is worth noting that the IOP profile in experimental glaucoma is different from that in human glaucoma. IOP spikes up to 50-60 mmHg are not uncommon following laser photocoagulation of the trabecular meshwork, which may induce ischemic injury to the retinal ganglion cells. ONH changes secondary to an acute IOP effect would be different from ONH deformation in chronic glaucoma.
A time window for therapeutic intervention may exist upon detection of ONH deformation before there is irreversible loss of retinal ganglion cells
We recently conducted a prospective study investigating the longitudinal profiles of ONH and RNFL changes in patients with glaucoma who had been followed for an average of 5.4 years (Xu et al., Ophthalmology 2014, In Press). In agreement with the experimental studies, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with reference to the HRT Topographic Change Analysis and OCT Guided Progression Analysis. The median lag time between observable ONH and RNFL changes was 15 months. These findings underscore the importance of detecting ONH surface depression for evaluation of glaucoma progression. A time window for therapeutic intervention may exist upon detection of ONH deformation before there is irreversible loss of retinal ganglion cells.
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