Dataset Information

Structure-Function Agreement Is Better Than Commonly Thought in Eyes With Early Glaucoma.

ABSTRACT: Purpose:To assess the agreement between structural (optical coherence tomography [OCT]) and functional (visual field [VF]) glaucomatous damage with an automated method and deviation/probability maps, and to compare this method to a metric method. Methods:Wide-field spectral-domain OCT scans, including the disc and macula, and 24-2 and 10-2 VFs were obtained from 45 healthy control (H) eyes/individuals, and 53 eyes/patients with 24-2 mean deviation (MD) better than -6 dB diagnosed as "definite glaucoma" (DG) by experts. Abnormal structure-abnormal function (aS-aF) agreement was assessed with an automated topographic (T) method based upon VF pattern deviation and OCT probability maps. Results were compared to a metric (M) method optimized for accuracy, (abnormal 24-2 glaucoma hemifield test [GHT] or pattern standard deviation [PSD], or 10-2 PSD AND abnormal OCT [quadrant]). Results:For the T-method, 47 (88.7%) of the 53 DG eyes showed aS-aF agreement, compared to 2 (4.5%) of the 45 H eyes. The aS-aF agreement for these two H eyes was easily identified as mistaken, and did not replicate on a subsequent test. Without the 10-2, the aS-aF agreement decreased from 47 to 34 (64.2%) of 53 DG eyes. For the M-method, 37 (69.8%) of the 53 DG eyes showed aS-aF agreement, while omitting the 10-2 VF resulted in agreement in only 33 (62.3%) eyes. Conclusions:There is good agreement between structural and functional damage, even in eyes with confirmed early glaucomatous damage, if both 24-2 and 10-2 VFs are obtained, and abnormal locations on the VFs are compared to abnormal regions seen on OCT macular and disc scans. This can be done in an objective, automated fashion. (ClinicalTrials.gov number, NCT02547740.).

SUBMITTER: Hood DC

PROVIDER: S-EPMC6860999 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Structure-Function Agreement Is Better Than Commonly Thought in Eyes With Early Glaucoma.

Hood Donald C DC Tsamis Emmanouil E Bommakanti Nikhil K NK Joiner Devon B DB Al-Aswad Lama A LA Blumberg Dana M DM Cioffi George A GA Liebmann Jeffrey M JM De Moraes Carlos G CG

Investigative ophthalmology & visual science 20191001 13

<h4>Purpose</h4>To assess the agreement between structural (optical coherence tomography [OCT]) and functional (visual field [VF]) glaucomatous damage with an automated method and deviation/probability maps, and to compare this method to a metric method.<h4>Methods</h4>Wide-field spectral-domain OCT scans, including the disc and macula, and 24-2 and 10-2 VFs were obtained from 45 healthy control (H) eyes/individuals, and 53 eyes/patients with 24-2 mean deviation (MD) better than -6 dB diagnosed ...[more]

PMID: 31618760

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Project description:Glaucoma is a multifactorial, neurodegenerative disease. The molecular mechanisms that underlie the pathophysiological changes in glaucomatous eyes, especially at the early stage of the disease, are poorly understood. Here, we report the findings from a quantitative proteomic analysis of retinas from experimental glaucoma (EG) eyes. An early stage of EG was modeled on unilateral eyes of five nonhuman primates (NHP) by laser treatment-induced elevation of intraocular pressure (IOP). Retinal proteins were extracted from individual EG eyes and their contralateral control eyes of the same animals, respectively, and analyzed by quantitative mass spectrometry (MS). As a result, a total, 475 retinal proteins were confidently identified and quantified. Results of bioinformatic analysis of proteins that showed an increase in the EG eyes suggested changes in apoptosis, DNA damage, immune response, cytoskeleton rearrangement and cell adhesion processes. Interestingly, hemoglobin subunit alpha (HBA) and Ras related C3 botulinum toxin substrate 1 (Rac1) were among the increased proteins. Results of molecular modeling of HBA- and Rac1-associated signaling network implicated the involvement of Mitogen-Activated Protein Kinase (MAPK) pathway in the EG, through which Rac1 may exert a regulatory role on HBA. This is the first observation of this potentially novel signaling network in the NHP retina and in EG. Results of Western blot analyses for Rac1, HBA and a selected MAPK pathway protein indicated synergistic changes in all three proteins in the EG eyes. Further, results of hierarchical cluster analysis of proteomes of control eyes revealed a clear age-proteome relationship, and such relationship appeared disrupted in the EG eyes. In conclusion, our results suggested an increased presence of a potentially novel signaling network at the early stage of glaucoma, and age might be one of the determinant factors in retinal proteomic characteristics under normal conditions.

Project description:PurposeTo evaluate optic nerve vascular density using swept source optical coherence tomography angiography (OCTA) in patients with early primary open angle glaucoma (POAG), pre-perimetric glaucoma and normal eyes.MethodsThis is a prospective, observational study including 56 eyes in total and divided into 3 groups; 20 eyes with mild POAG, 20 pre-perimetric glaucoma eyes, and 16 age-matched normal eyes as controls. The optic disc region was imaged by a 1050-nm-wavelength swept-source OCT system (DRI OCT Triton, TOPCON). Vessel density was assessed as the ratio of the area occupied by the vessels in 3 distinct regions: 1) within the optic nerve head; 2) in the 3 mm papillary region around the optic disc; and 3) in the peripapillary region, defined as a 700-?m-wide elliptical annulus around the disc. The potential associations between vessel density and structural, functional measures were analyzed.ResultsThere was a statistically significant difference for the peripapillary vessel density, optic nerve head vessel density, and papillary vessel density among all the groups (p<0.001). Control eyes showed a significant difference for all measured vessel densities compared to glaucomatous eyes (p values from 0.001 to 0.024). There was a statistically significant difference between control and pre-perimetric glaucoma eyes for peripapillary, optic nerve head and papillary vessel density values (p values from 0.001 to 0.007). The optic nerve head vessel density, superior and inferior papillary area vessel density (Pearson r = 0.512, 0.436, 0.523 respectively) were highly correlated with mean overall, superior and inferior RNFL thickness in POAG eyes (p = 0.04, p = 0.02 and p = 0.04 respectively). Multiple linear regression analysis of POAG group showed that optic nerve head vessel density in POAG group was more strongly linked to RNFL thickness than to any other variables.ConclusionsEyes with mild POAG could be differentiated from pre-perimetric glaucoma eyes, which also could be differentiated from normal eyes using OCTA-derived retinal vessel density measurements.

Project description:PurposeTo investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline.DesignLongitudinal cohort study.ParticipantsA total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected.MethodsOCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity.Main outcome measuresMagnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time.ResultsThe median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding.ConclusionsCorrelations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

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Structure-Function Agreement Is Better Than Commonly Thought in Eyes With Early Glaucoma.

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Structure-Function Agreement Is Better Than Commonly Thought in Eyes With Early Glaucoma.

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