Early localized alterations of the retinal inner plexiform layer in association with visual field worsening in glaucoma patients

• Published in: PloS one Vol. 16; no. 2; p. e0247401
• Main Authors: Aydın, Rukiye, Barış, Mine, Durmaz-Engin, Ceren, Al-Aswad, Lama A., Blumberg, Dana M., Cioffi, George A., Liebmann, Jeffrey M., Tezel, Tongalp H., Tezel, Gülgün
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.02.2021; Public Library of Science (PLoS)
• Subjects: Acuity; Aged; Aged, 80 and over; Amacrine Cells - pathology; Automation; Biology and Life Sciences; Blindness; Blindness - pathology; Cataracts; Cornea; Dendrites; Diabetic retinopathy; Diagnosis; Disease; Drafting software; Error analysis; Error correction; Female; Glaucoma; Glaucoma, Open-Angle - pathology; Health aspects; Humans; Injury prevention; Intraocular pressure; Intraocular Pressure - physiology; Macula Lutea - pathology; Male; Measurement; Medical personnel; Medicine and Health Sciences; Middle Aged; Nerve Fibers - pathology; Ophthalmology; Optic Nerve - pathology; Physicians; Physiological aspects; Pressure measurement; Research and Analysis Methods; Retina; Retinal ganglion cells; Retinal Ganglion Cells - pathology; Retrospective Studies; Rewiring; Social Sciences; Surgeons; Synaptic plasticity; Thickness measurement; Tomography, Optical Coherence - methods; Visual acuity; Visual field; Visual Field Tests - methods; Visual fields; Visual Fields - physiology; United States; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0247401

Glaucoma is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness, worldwide. While the experimental research using animal models provides growing information about cellular and molecular processes, parallel analysis of the clinical presentation of glaucoma accelerates the translational progress towards improved understanding, treatment, and clinical testing of glaucoma. Optic nerve axon injury triggers early alterations of retinal ganglion cell (RGC) synapses with function deficits prior to manifest RGC loss in animal models of glaucoma. For testing the clinical relevance of experimental observations, this study analyzed the functional correlation of localized alterations in the inner plexiform layer (IPL), where RGCs establish synaptic connections with retinal bipolar and amacrine cells. Participants of the study included a retrospective cohort of 36 eyes with glaucoma and a control group of 18 non-glaucomatous subjects followed for two-years. The IPL was analyzed on consecutively collected macular SD-OCT scans, and functional correlations with corresponding 10–2 visual field scores were tested using generalized estimating equations (GEE) models. The GEE-estimated rate of decrease in IPL thickness (R = 0.36, P<0.001) and IPL density (R = 0.36, P<0.001), as opposed to unchanged or increased IPL thickness or density, was significantly associated with visual field worsening at corresponding analysis locations. Based on multivariate logistic regression analysis, this association was independent from the patients’ age, the baseline visual field scores, or the baseline thickness or alterations of retinal nerve fiber or RGC layers (P>0.05). These findings support early localized IPL alterations in correlation with progressing visual field defects in glaucomatous eyes. Considering the experimental data, glaucoma-related increase in IPL thickness/density might reflect dendritic remodeling, mitochondrial redistribution, and glial responses for synapse maintenance, but decreased IPL thickness/density might correspond to dendrite atrophy. The bridging of experimental data with clinical findings encourages further research along the translational path.