Contributions of Brain Microstructures and Metabolism to Visual Field Loss Patterns in Glaucoma Using Archetypal and Information Gain Analyses

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2024 Jul 8

PMID 38975942

Authors

Yueyin Pang

Ji Won Bang

Anisha Kasi

Jeremy Li

Carlos Parra

Els Fieremans

Gadi Wollstein

Joel S Schuman

Mengyu Wang

Kevin C Chan

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures.

Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma.

Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma.

Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.

References

Sponsel W, Groth S, Satsangi N, Maddess T, Reilly M . Refined Data Analysis Provides Clinical Evidence for Central Nervous System Control of Chronic Glaucomatous Neurodegeneration. Transl Vis Sci Technol. 2014; 3(3):1. PMC: 4043108. DOI: 10.1167/tvst.3.3.1. View

Tran V, Saad T, Tesfaye M, Walelign S, Wordofa M, Abera D . Helicobacter pylori (H. pylori) risk factor analysis and prevalence prediction: a machine learning-based approach. BMC Infect Dis. 2022; 22(1):655. PMC: 9330977. DOI: 10.1186/s12879-022-07625-7. View

Hoste A . New insights into the subjective perception of visual field defects. Bull Soc Belge Ophtalmol. 2003; (287):65-71. View

Sun Z, Parra C, Bang J, Fieremans E, Wollstein G, Schuman J . Diffusion Kurtosis Imaging Reveals Optic Tract Damage That Correlates with Clinical Severity in Glaucoma. Annu Int Conf IEEE Eng Med Biol Soc. 2020; 2020:1746-1749. PMC: 8163524. DOI: 10.1109/EMBC44109.2020.9176192. View

Saionz E, Busza A, Huxlin K . Rehabilitation of visual perception in cortical blindness. Handb Clin Neurol. 2022; 184:357-373. PMC: 9682408. DOI: 10.1016/B978-0-12-819410-2.00030-8. View

Yang X, Van der Merwe Y, Sims J, Parra C, Ho L, Schuman J . Age-related Changes in Eye, Brain and Visuomotor Behavior in the DBA/2J Mouse Model of Chronic Glaucoma. Sci Rep. 2018; 8(1):4643. PMC: 5854610. DOI: 10.1038/s41598-018-22850-4. View

Chan R, Bang J, Trivedi V, Murphy M, Liu P, Wollstein G . Relationships between cerebrovascular reactivity, visual-evoked functional activity, and resting-state functional connectivity in the visual cortex and basal forebrain in glaucoma. Annu Int Conf IEEE Eng Med Biol Soc. 2021; 2021:4037-4040. PMC: 9218998. DOI: 10.1109/EMBC46164.2021.9630904. View

Wang M, Shen L, Pasquale L, Boland M, Wellik S, De Moraes C . Artificial Intelligence Classification of Central Visual Field Patterns in Glaucoma. Ophthalmology. 2020; 127(6):731-738. PMC: 7246163. DOI: 10.1016/j.ophtha.2019.12.004. View

Faiq M, Sengupta T, Nath M, Velpandian T, Saluja D, Dada R . Ocular manifestations of central insulin resistance. Neural Regen Res. 2022; 18(5):1139-1146. PMC: 9827783. DOI: 10.4103/1673-5374.355765. View

10.

Bang J, Parra C, Yu K, Wollstein G, Schuman J, Chan K . GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients. Commun Biol. 2023; 6(1):679. PMC: 10310759. DOI: 10.1038/s42003-023-04918-8. View

11.

Stagg C, Bachtiar V, Johansen-Berg H . What are we measuring with GABA magnetic resonance spectroscopy?. Commun Integr Biol. 2011; 4(5):573-5. PMC: 3204132. DOI: 10.4161/cib.4.5.16213. View

12.

You Y, Joseph C, Wang C, Gupta V, Liu S, Yiannikas C . Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease. Brain. 2019; 142(2):426-442. DOI: 10.1093/brain/awy338. View

13.

Kim U, Mahroo O, Mollon J, Yu-Wai-Man P . Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance. Front Neurol. 2021; 12:661938. PMC: 8175861. DOI: 10.3389/fneur.2021.661938. View

14.

Gonzalez Fleitas M, Devouassoux J, Aranda M, Dieguez H, Calanni J, Iaquinandi A . Melatonin Prevents Non-image-Forming Visual System Alterations Induced by Experimental Glaucoma in Rats. Mol Neurobiol. 2021; 58(8):3653-3664. DOI: 10.1007/s12035-021-02374-1. View

15.

Keltner J, Johnson C, Cello K, Edwards M, Bandermann S, Kass M . Classification of visual field abnormalities in the ocular hypertension treatment study. Arch Ophthalmol. 2003; 121(5):643-50. DOI: 10.1001/archopht.121.5.643. View

16.

Yucel Y, Gupta N . Glaucoma of the brain: a disease model for the study of transsynaptic neural degeneration. Prog Brain Res. 2008; 173:465-78. DOI: 10.1016/S0079-6123(08)01132-1. View

17.

Van der Merwe Y, Murphy M, Sims J, Faiq M, Yang X, Ho L . Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control. Neurotherapeutics. 2021; 18(2):1339-1359. PMC: 8423893. DOI: 10.1007/s13311-021-01033-6. View

18.

Wang M, Tichelaar J, Pasquale L, Shen L, Boland M, Wellik S . Characterization of Central Visual Field Loss in End-stage Glaucoma by Unsupervised Artificial Intelligence. JAMA Ophthalmol. 2020; 138(2):190-198. PMC: 6990977. DOI: 10.1001/jamaophthalmol.2019.5413. View

19.

Berdahl J, Allingham R . Intracranial pressure and glaucoma. Curr Opin Ophthalmol. 2009; 21(2):106-11. DOI: 10.1097/ICU.0b013e32833651d8. View

20.

Reilly M, Villarreal A, Maddess T, Sponsel W . Refined Frequency Doubling Perimetry Analysis Reaffirms Central Nervous System Control of Chronic Glaucomatous Neurodegeneration. Transl Vis Sci Technol. 2015; 4(3):7. PMC: 4461216. DOI: 10.1167/tvst.4.3.7. View