Retinal putative glial alterations: implication for glaucoma care

Abstract

PurposeGliosis‐like retinal alterations, presumed to be activated retinal astrocytes and Müller cells (ARAM), have been reported to occur frequently in patients with glaucoma but rarely in controls. We investigated the association between glaucomatous abnormality and the presence, the extent of retinal region, and the spatial distribution, of hyperreflective retinal alterations on optical coherence tomography (OCT) en‐face images, presumed to be ARAM.MethodsFindings of hyperreflective structures, presumed to be ARAM, in the central retinal ±24 degrees of OCT en‐face images (acquired with the SPECTRALIS® OCT) were compared between 35 younger controls, 42 older controls and 38 patients with glaucoma. Presumed ARAM was defined as reflective structures on the en‐face images other than retinal vasculature and retinal nerve fibre bundles. Chi‐square tests were used to compare the proportion of younger controls vs older controls with presumed ARAM to investigate the effect of ageing, and the proportion of patients vs age‐similar older controls with presumed ARAM to investigate the effect of disease. We also investigated the effect of glaucoma on the retinal area with presumed ARAM when it was present; we used an analysis of covariance (ancova) to compare the retinal area with hyperreflectivity in patients vs controls, adjusting for the effects of age and axial length.ResultsThe mean (S.D.) age of the younger controls, older controls, and patients with glaucoma was 26 (3), 62 (10) and 69 (8) years, respectively. The median (25th quartile, 75th quartile) of the retinal region with the hyperreflective structures, presumed to be ARAM, was zero (0,0), 1 (0,6), and 11 (0,43) degrees square in the younger controls, older controls and patients with glaucoma respectively. The chi‐square test investigating the effect of ageing found χ2(1, N = 77) = 24.8, p < 0.001, and that investigating the effect of disease found χ2(1, N = 80) = 2.3, p = 0.1. The ancova found F(1, 46) = 10.32, P = 0.02.ConclusionsThere was an effect of ageing on the presence of the hyperreflective structures, presumed to be ARAM, on OCT images. Compared to the presence of hyperreflective structures, the extent of retinal region with the hyperreflective structures has a greater potential of being an indicator of glaucomatous degeneration. Further study is needed to investigate the nature of the relation between glaucomatous abnormality and the extent of the retina with the hyperreflective structures, presumed to be ARAM.

Presumed activated retinal astrocytes and Müller cells in healthy and glaucomatous eyes detected by spectral domain optical coherence tomography

“…7 Nutzi et al concluded there was no effect of age in a group of 12 patients with an average age of 77.6 AE 7.2 years. 17 In agreement with Ashimatey et al, 8 the present study found a significant age effect. Additionally, ARAM was noted in healthy age-similar controls at similar frequencies to patients with glaucoma.…”

“…• Higher density of ARAM in an eye may be a clinical and structural sign for more advanced glaucoma • ARAM was found in 55% of older controls but not in younger controls, showing an age effect • ARAM was found in 73% of patients with glaucoma • Patients with glaucoma tend to have larger retinal areas with ARAM • Extent of ARAM and its distribution was not predictive of retinal hemifield with the most damage • ARAM was found in 15% to 16% of healthy controls • ARAM was found in 15% to 23% of patients • ARAM was found in 17% to 19% of age-similar sex-matched healthy controls • ARAM was found to be related to age as well as posterior vitreous detachment • ARAM was not found to be related to sex continuous variable such as quantifying the percentage area covered by ARAM may be more helpful, as it has previously been identified as a potential biomarker for retinal ganglion cell (RGC) health 15 and the severity of glaucomatous damage. 8,17 To resolve the relationship of ARAM to glaucoma, and especially to the severity of glaucoma, including subjects with more advanced glaucomatous disease would be informative.…”

“…15 This is supported by recent studies investigating the relationship between activated glia and glaucoma. 8,17 Edwards et al characterised idiopathic preretinal glia immunohistochemically and identified both M€ uller cells and astrocytes in these preretinal glial projections and membranes. They found a high level of glial activation at vitreous attachment sites.…”

Macular Inner Retinal Layer Thickness in Relation to Photopic and Mesopic Contrast Sensitivity in Healthy Young and Older Subjects

“…In older individuals and glaucoma patients, hyperreflective structures (activated retinal astrocytes and Müller cells) seen on OCT en face imaging (cpRNFL) are common, whereas these structures are scarce in younger individuals. 34 Also, in primary open-angle glaucoma, these hyperreflective structures have been more frequently identified in eyes showing lower retinal sensitivity and cpRNFL thickness. 35 In our younger subjects, photopic CS showed significant correlation with the thickness measurements of peripheral macular IRL, GCC and cpRNFL (Table 2).…”

Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma

“…Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness worldwide [1]. While this condition is primarily characterised by the loss of retinal ganglion cells (RGCs) and the gradual degeneration of RGC axons in the optic nerve [2], recent morphological and functional studies have suggested the involvement of other retinal cell types, including atrophic changes in the photoreceptor layer and microglia activation [3][4][5]. At present, intraocular pressure (IOP) is the major clinically modifiable risk factor for glaucoma progression (vision loss) and current therapies seek to modulate IOP via reducing aqueous production or increasing outflow [6].…”