Abstract
Purpose To link the clinically defined retinal and perceptual deficits in glaucoma by quantifying optic nerve structural integrity in the human visual system.
Methods We characterized optic nerve (ON) neuropathy in patients with unilateral glaucoma (n = 6) using probabilistic diffusion weighted imaging (DWI) tractography.
Results Glaucoma was associated with reduced structural integrity of the optic nerves. Specifically, we found reduced fractional anisotropy in the ONs of eyes with advanced, as compared to mild, stages of disease (F(1,10) = 55.474, p < 0.00001). Furthermore, by comparing the ratios of ON fractional anisotropies in glaucoma subjects to those of healthy controls (n = 6) we determined that this difference was beyond that expected from normal anatomical variation (F(1,9) = 20.276, p < 0. 005). Finally, we linked neural integrity to clinical assessments. Retinal measures (vertical cup-to-disc ratio) predicted optic nerve neural integrity (ON FA) (F(1,10) = 11.061, p < 0.01), and neural integrity in turn predicted perceptual performance (visual field index (VFI)) (F(1,10) = 15.308, p < 0.005).
Conclusion We provide methods to detect glaucoma-related structural changes in the optic nerves and establish that the retinal, neural, and perceptual measures of glaucoma are well-correlated.
Translational Relevance We demonstrate the potential of diffusion MRI as a clinical tool in human glaucoma. Early detection is critical given the degenerative nature of the disease, and the availability of additional diagnostic tools such as dMRI may significantly improve treatment outcome.
Precis Glaucoma is the leading cause of irreversible vision loss. Here we link clinical measures of optic nerve structure and function to diffusion magnetic resonance imaging (dMRI) measures of optic nerve integrity. These results will help improve the early diagnosis and treatment of glaucoma.
Funding: This research was funded in part by an institutional grant from Research to Prevent Blindness to the University of Wisconsin-Madison Dept. of Ophthalmology and Visual Sciences.
Acknowledgements
We thank Anna Bauman for assistance with patient recruitment and data collection and Franco Pestilli for comments that greatly improved the manuscript.