Longitudinal changes in superficial microvasculature in glaucomatous retinal nerve fiber layer defects after disc hemorrhage
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SUBMITTER: Okamoto Y
PROVIDER: S-EPMC7744505 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:PurposeTo estimate retinal ganglion cell (RGC) losses associated with visible glaucomatous localized retinal nerve fiber layer (RNFL) defects.DesignObservational cross-sectional study.MethodsA multicenter study of 198 normal eyes (138 subjects) and 66 glaucomatous eyes (55 subjects) recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All eyes underwent standard automated perimetry (SAP), spectral-domain optical coherence tomography, and fundus stereophotography within 6 months. Glaucomatous eyes were included if localized RNFL defects were detected by masked grading of stereophotographs. The number of RGCs in each sector of a structure-function map was estimated using a previously published model combining RGC estimates from SAP and spectral-domain optical coherence tomography. The estimated percentage loss of RGCs (combined structure-function index) was calculated.ResultsIn glaucomatous eyes, there were 136 sectors with visible RNFL defects and 524 sectors without visible RNFL defects. The most common sectors with visible RNFL defects were inferior and inferotemporal sectors, followed by superior and supertemporal sectors. Eyes with visible RNFL defects had a mean estimated RGC count of 657,172 cells versus 968 883 cells in healthy eyes (P < .001). The average combined structure-function index in sectors with a visible RNFL defect (59 ± 21%) was significantly higher than in sectors without a visible RNFL defect in glaucomatous eyes (15 ± 29%; P < .001) and higher than in healthy eyes (1 ± 13%; P < .001).ConclusionsAlthough visible localized RNFL defects often are considered an early sign of glaucoma, this study indicates that they are likely to be associated with large neuronal losses.
| S-EPMC3764310 | biostudies-literature
Project description:To investigate macular ganglion cell-inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs.112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 ?m versus 79.2 ± 6.6 ?m respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 ?m, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect.The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.
| S-EPMC4990273 | biostudies-literature
Project description:PurposeDescribe a new method to analyze retinal nerve fiber layer (RNFL) thickness maps.DesignCross-sectional study.SubjectsRNFL thickness maps of healthy and glaucomatous eyes.MethodsOptical coherence tomography (OCT) RNFL raster scans from 98 healthy and 50 glaucomatous eyes were analyzed. The RNFL thickness maps were separated into superficial (SNFL) and deep (DNFL) slabs through a partial thickness plane set at the modal thickness (mode). Association between mode and OCT signal strength (SS), age, axial length, and visual field mean deviation (VFMD) was tested (Pearson coefficient, r). Thicknesses of inferior and superior SNFL regions (i-,s-SNFL), and inferior, superior, nasal, and temporal DNFL regions (i-,s-,n-,t-DNFL) were calculated. The regions thicknesses were compared between healthy and glaucomatous eyes (t-test) and between glaucomatous eyes with early, moderate, and severe disease (ANOVA and linear regressions of thickness on VFMD). Diagnostic accuracy and correlation with VFMD of RNFL regions thicknesses were calculated as the area under the receiver operating characteristic curve (AUC) and Pearson r, respectively. P<0.05 was considered significant.Main outcomeThickness of regions in SNFL and DNFL slabs.ResultsThe mode was not associated with SS, age, axial length, or VFMD, it circumscribed the thicker RNFL around the optic disc of healthy and glaucomatous eyes, and it was used to separate the SNFL and DNFL slabs of RNFL thickness maps. The thickness of the SNFL slab was less in glaucomatous eyes than in healthy eyes (P<0.001). S-SNFL and i-SNFL thicknesses (respectively) were 86.0±8.2μm and 87.3±9.6μm in healthy eyes vs. 66.1±9.1μm and 63.4±8.2μm in glaucomatous eyes (P<0.001 for both). The thickness of the DNFL slab was similar between groups (P=0.19). T-DNFL thickness was 37.0±5.3μm in healthy eyes vs. 33.9±5.0μm in glaucomatous eyes (P<0.001); thicknesses of all other DNFL regions were similar. The SNFL regions only thinned with progressively worse glaucoma severity, had excellent AUCs (AUC≥0.95, P<0.001), and correlated strongly with VFMD (r≥0.60, P<0.001).ConclusionsGlaucomatous RNFL thinning is predominantly detected within a slab with thickness greater than the mode. SNFL thickness has great AUC and correlation with VFMD in glaucomatous eyes. The usefulness for diagnosis and monitoring of glaucoma needs further study.
| S-EPMC7337289 | biostudies-literature
Project description:PurposeCircumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT.MethodsA longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test.ResultsThere were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models.ConclusionsOur results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms.Translational relevanceUnderstanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.
| S-EPMC10584025 | biostudies-literature
Project description:Multiple retinal nerve fiber layer (RNFL) defects develop uncommonly, even though glaucomatous RNFL loss is typically observed as one RNFL defect in each quadrant. We investigated the risk factors associated with multiple RNFL defects to increase our understanding of the nature and pathogenesis of various RNFL defect patterns. Data from subjects with multiple RNFL defects (28 patients) and glaucoma patients without multiple RNFL defects (194 patients) were analyzed. The term "multiple RNFL defects" refers to three or more isolated defects separated by a comparatively normal area. Patients with multiple RNFL defects showed a higher prevalence of hypertension, end-stage renal disease, and cerebrovascular disease than those without multiple RNFL defects, both before and after propensity score matching for age and mean deviation (all P?<?0.05). The number of patients with parafoveal visual field points depressed <5% on pattern deviation plots was higher in subjects with multiple RNFL defects than in those without multiple RNFL defects (P?=?0.048). In conclusion, the presence of multiple RNFL defects had clinical relevance for systemic vascular risk factors and a higher risk of parafoveal scotoma. Clinicians should be aware of the possibility of concomitant systemic vascular disease when evaluating patients with multiple RNFL defects.
| S-EPMC5958060 | biostudies-literature
Project description:ObjectiveTo examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors.DesignRetrospective, cross-sectional, observational study.MethodsTwo hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area.ResultsMicrocystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions.ConclusionsMicrocystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.
| S-EPMC4467090 | biostudies-literature
Project description:PurposeTo assess the effects of local defects, segmentation errors, and improper image alignment on the performance of the commonly used optical coherence tomography (OCT) measure of progression, that is the change in global (average) circumpapillary retinal nerve fiber layer (cpRNFL) thickness (ΔG).MethodsOne hundred fifty eyes suspected of, or with, early glaucoma had OCT circle and cube scans obtained using eye tracking on two occasions at least 1 year apart. Statistical progression was defined by fixed values of ΔG (3-8 um) and quantile regression. For a reference standard, four authors identified 30 eyes as "likely progressed," and 61 eyes that "likely had not progressed" based on OCT reports from both baseline and follow-up tests.ResultsA ΔG criterion of 4 um had the best accuracy: 77%, with 5 false positive (8.2%) and 16 false negative (53%). A post hoc analysis of circular b-scans and OCT probability maps of these eyes indicated that segmentation errors and local progression accounted for most of these mistakes. Segmentation errors, although less common, were also present in true positives and true negatives.ConclusionsLocal defects and segmentation errors are the primary reasons for the poor performance of cpRNFL thickness G metric. Because these problems are difficult, if not impossible, to eliminate, the G metric should not be relied on in isolation for detecting glaucomatous progression.Translational relevanceLocal defects and segmentation errors are easily identified by viewing OCT circumpapillary images, which should be part of the standard protocol for detecting glaucomatous progression.
| S-EPMC7585398 | biostudies-literature
Project description:Importance:Parapapillary choroidal microvasculature dropout (MvD) is considered one of pathophysiological manifestations of glaucomatous damage. Objective:To evaluate the longitudinal change in the parapapillary choroidal MvD in patients with primary open-angle glaucoma (POAG), and to determine whether this change is associated with progressive retinal nerve fiber layer (RNFL) thinning. Design, Setting, and Participants:This prospective observational case series was conducted at a tertiary referral center in Korea and included 68 patients with POAG who exhibited parapapillary choroidal MvD in en face optical coherence tomography (OCT) angiography (OCTA) images who were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2016, through July 31, 2018. The mean (SD) follow-up period was 2.5 (0.2) years and observers were masked to the clinical characteristics of the participants for measurements. The OCTA images were obtained twice at an interval of at least 2 years, during which the RNFL thickness was measured at least 4 times in serial OCT examinations. Microvasculature dropout was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. The MvD area was measured in the OCTA images obtained at the baseline and the final follow-up. The significance of changes in the MvD area was defined using the 95% Bland-Altman limits of agreement. The rate of RNFL thinning was determined by linear regression of the serial OCT RNFL thickness measurements. Main Outcomes and Measures:The association between the change in the MvD area and the rate of RNFL thinning. Results:Of 68 Korean participants, 37 (54.5%) were women, and the mean (SD) age was 54.3 (13.1) years. Among 68 eyes, 22 (32.4%) showed increases in the MvD area during the follow-up. Faster global RNFL thinning was associated with a larger baseline parapapillary atrophy β-zone (β = -0.55; 95% CI, -0.96 to -0.14; P = .01), disc hemorrhage detection during the follow-up period (β = -0.75; 95% CI, -1.67 to -0.34; P = .001), and a larger increase in the MvD area (β = -4.74; 95% CI, -7.72 to -1.75; P = .002). The MvD area was not associated with the rate of RNFL thinning at baseline or the final follow-up. Conclusions and Relevance:Microvasculature dropout enlargement was associated with progressive RNFL thinning in POAG.
| S-EPMC6547096 | biostudies-literature
Project description:To determine whether focal abnormalities of the lamina cribrosa (LC) are present in glaucomatous eyes with localized retinal nerve fiber layer (RNFL) defects.Cross-sectional, observational study.We analyzed 20 eyes of 14 subjects with localized RNFL defects detected by masked grading of stereophotographs and 40 eyes of 25 age-matched healthy subjects recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego.All eyes had stereoscopic optic disc photography and in vivo LC imaging using enhanced depth imaging optical coherence tomography (EDI-OCT). Two masked graders identified focal LC defects defined by a standardized protocol using 48 radial scan EDI-OCT images. The kappa coefficient was calculated as a measure of the reliability of interobserver agreement.The number of focal LC defects and the relationship between the location of LC defects and the location of localized RNFL defects.Of 20 eyes with a localized RNFL defect, 15 (75%) had ?1 LC defect compared with only 1 of 40 healthy eyes (3%). There were 13 eyes with localized RNFL defects that had 1 LC defect, 1 eye with 2 LC defects, and 1eye with 3 LC defects. The largest area LC defect was present in a radial line EDI-OCT scan corresponding with a localized RNFL defect in 13 of 15 eyes (87%). There was good agreement between graders as to whether an eye had an LC defect (kappa = 0.87; 95% confidence interval [CI], 0.73-1.00; P<0.001) and the location of the largest defect (kappa = 0.72; 95% CI, 0.44-1.00; P<0.001).Focal defects of the LC were frequently visible in glaucomatous eyes with localized RNFL defects. Focal abnormalities of the LC may be associated with focal retinal nerve fiber damage.
| S-EPMC3947348 | biostudies-literature
Project description:Importance:Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. Objectives:To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. Design, Setting, and Participants:This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Main Outcomes and Measures:Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. Results:The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] μm/y; difference, -0.43 [-0.76 to -0.09] μm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] μm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (β2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (β2, -0.05 [95% CI, -0.17 to 0.06], P = .36). Conclusions and Relevance:These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.
| S-EPMC6459105 | biostudies-literature