Alteraciones en el nervio óptico y retina en pacientes con COVID-19. Una revisión teórica / Alterations in the optic nerve and retina in patients with COVID-19. A theoretical review

El objetivo de la presente investigación es identificar y sistematizar las afectaciones generadas por el SARS-CoV-2 en el nervio óptico y en la retina de pacientes jóvenes, adultos y adultos mayores que padecieron COVID-19 en el período del 2019 al 2022. Se realizó una revisión teórica documental (RTD) en el marco de una investigación para determinar el estado actual del conocimiento del tema objeto de estudio. La RTD contempla el análisis de publicaciones en las bases de datos científicas PubMed/Medline, Ebsco, Scielo y Google. Se encontraron un total de 167 artículos de los cuales se estudiaron a profundidad 56 artículos; se evidencia el impacto de la infección por COVID-19 en la retina y el nervio óptico de los pacientes contagiados, tanto durante la fase aguda como en la recuperación posterior. Entre los hallazgos reportados sobresalen: neuropatía óptica isquémica no arterítica anterior y posterior, neuritis óptica, oclusión vascular central o de rama, maculopatía medial aguda paracentral, neurorretinitis, así como también diagnósticos concomitantes como enfermedad posible de Vogt Koyanagi Harada, síndrome de múltiples puntos blancos evanescentes (MEWDS), retinopatía Purtscher-like, y otros (AU)

The objective of this research is to identify and systematize the medical conditions generated by SARS-CoV-2 on the optic nerve and retina of young, adult, and elderly adults who suffered from COVID-19 in the period 2019-2022. A theoretical documentary review (TDR) was conducted within the framework of an investigation to determine the current state of knowledge of the subject under study. The TDR includes the analysis of publications in the scientific databases PubMed/Medline, Ebsco, Scielo and Google. A total of 167 articles were found, of which 56 were studied in depth, and these evidence the impact of COVID-19 infection on the retina and optic nerve of infected patients, both during the acute phase and in subsequent recovery. Among the reported findings, the following stand out: anterior and posterior non-arteritic ischemic optic neuropathy, optic neuritis, central or branch vascular occlusion, paracentral acute medial maculopathy, neuroretinitis, as well as concomitant diagnoses such as possible Vogt-Koyanagi-Harada disease, multiple evanescent white dot syndrome (MEWDS), Purtscher-like retinopathy, among others (AU)

Deep learning assisted detection of glaucomatous optic neuropathy and potential designs for a generalizable model.

PURPOSE: To evaluate ways to improve the generalizability of a deep learning algorithm for identifying glaucomatous optic neuropathy (GON) using a limited number of fundus photographs, as well as the key features being used for classification. METHODS: A total of 944 fundus images from Taipei Veterans General Hospital (TVGH) were retrospectively collected. Clinical and demographic characteristics, including structural and functional measurements of the images with GON, were recorded. Transfer learning based on VGGNet was used to construct a convolutional neural network (CNN) to identify GON. To avoid missing cases with advanced GON, an ensemble model was adopted in which a support vector machine classifier would make final classification based on cup-to-disc ratio if the CNN classifier had low-confidence score. The CNN classifier was first established using TVGH dataset, and then fine-tuned by combining the training images of TVGH and Drishti-GS datasets. Class activation map (CAM) was used to identify key features used for CNN classification. Performance of each classifier was determined through area under receiver operating characteristic curve (AUC) and compared with the ensemble model by diagnostic accuracy. RESULTS: In 187 TVGH test images, the accuracy, sensitivity, and specificity of the CNN classifier were 95.0%, 95.7%, and 94.2%, respectively, and the AUC was 0.992 compared to the 92.8% accuracy rate of the ensemble model. For the Drishti-GS test images, the accuracy of the CNN, the fine-tuned CNN and ensemble model was 33.3%, 80.3%, and 80.3%, respectively. The CNN classifier did not misclassify images with moderate to severe diseases. Class-discriminative regions revealed by CAM co-localized with known characteristics of GON. CONCLUSIONS: The ensemble model or a fine-tuned CNN classifier may be potential designs to build a generalizable deep learning model for glaucoma detection when large image databases are not available.

Optic disc hemorrhages in glaucoma and common clinical features.

OBJECTIVE: To analyze optic nerve head stereophotographs for the presence of optic disc hemorrhages, and to describe bleeding patterns and patient characteristics. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: 1113 optic nerve stereophotograph pairs of 562 consecutive patients. METHODS: Stereophotographs were systematically reviewed for the presence of a disc hemorrhage with careful documentation of optic nerve head features. All charts of patients with hemorrhage were subsequently studied for demographic information and clinical data. RESULTS: Disc hemorrhages were observed in 7.1% of patients with optic disc photography. Most patients had open-angle glaucoma (57.5%) with focal ischemic phenotype of the optic disc (66.7%). The mean vertical and horizontal cup-disc ratios were 0.82 ± 0.14 and 0.76 ± 0.14, respectively. The ß-zone peripapillary atrophy was observed in 48.9% of patients. The most common location was the inferotemporal region of the disc (60.8%), and most were flame or splinter shaped (70.6%). Disc hemorrhages were found either superficial to or within the retinal nerve fibre layer (72.5%), and in association with a notch (64.4%). The average intraocular pressure was 17.3 ± 4.9 mm Hg, and most hemorrhages were associated with early visual field defects (42.5%). CONCLUSIONS: Optic disc hemorrhages in patients with glaucoma were most frequently observed inferiorly in association with a notch. Most eyes with a disc hemorrhage had an intraocular pressure within normal range and had either early or no visual field loss. These findings highlight the importance of careful examination of the optic nerve head to look for the presence of a disc hemorrhage as an important biomarker of glaucoma damage.

Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema.

PURPOSE: To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE). DESIGN: Prospective observational study. SUBJECTS: Nineteen children between the ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included. METHODS: All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality. MAIN OUTCOME MEASURES: Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE. RESULTS: Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%-100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%-70%) of misinterpretation of PE as PPE. CONCLUSIONS: The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.

Peripapillary perfused capillary density in primary open-angle glaucoma across disease stage: an optical coherence tomography angiography study.

AIMS: To assess peripapillary perfused capillary density (PCD) in primary open-angle glaucoma (POAG) across stage of disease. METHODS: In this observational, cross-sectional study, 60 eyes with varying stages of POAG and 24 control eyes were imaged on a spectral domain optical coherence tomography angiography system (AngioVue, Optovue, Fremont, California, USA) generating images centred on the optic nerve head. Major blood vessels were removed using custom automated software. PCD was calculated as a percentage as the ratio of pixels associated with perfused capillaries to the total number of pixels in the corresponding region-of-interest (ROI). Analysis of covariance was used to compare PCD among the subject groups and control for possible covariates. Area under the receiver operating characteristic curve (AROC) and sensitivity at 95% specificity were calculated to assess the capability of PCD to distinguish mild glaucoma from control. The Pearson's product-moment correlation coefficient was used to assess correlations between PCD and circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and visual field mean deviation (MD). RESULTS: PCD demonstrated a progressive stepwise decrease from control eyes throughout worsening POAG stage at all ROIs. PCD demonstrated AROC and sensitivity values comparable to cpRNFLT and visual field parameters and exhibited significant correlations with cpRNFLT and MD at all corresponding ROIs. CONCLUSIONS: PCD displayed significant correlations with morphological and functional indices and exhibited diagnostic capabilities comparable to currently employed clinical variables. Our preliminary results suggest that PCD analysis may prove to be a useful tool in monitoring POAG across stage and identifying early POAG.

Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic.

PURPOSE: To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns. MATERIALS AND METHODS: For each of 16 previously identified VF loss patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10-20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test. RESULTS: 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often ≥ 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often < 0.7 among eyes representative of AT1 (no focal defect; p < 0.001) and AT2 (superior defect; p = 0.027), which was also associated with ptosis (p < 0.001). AT12 (temporal hemianopia) was associated with history of stroke (p = 0.022). AT11 (concentric peripheral defect) trended toward association with trial lens correction > 6D (p = 0.069). CONCLUSIONS: Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.

Structure-Functional Parameters in Differentiating Between Patients With Different Degrees of Glaucoma.

PURPOSE: We evaluated spectral-domain optical coherence tomography (SD-OCT) parameters and visual field parameters in patients with different degrees of open-angle glaucoma (preperimetric, mild, moderate, and severe glaucoma) to determine which parameter best identifies each glaucomatous group. MATERIALS AND METHODS: A total of 131 patients (66 preperimetric, 41 mild, 35 moderate, 40 severe glaucomatous eyes) and 40 normal eyes (control group) were included in this prospective study. The SD-OCT parameters [mean ganglion cell complex (GCC), superior GCC, inferior GCC, global loss volume, focal loss volume, mean circumpapillary retinal nerve fiber layer (RNFL), superior circumpapillary retinal nerve fiber layer [cpRNFL], and inferior cpRNFL] and visual field parameters (mean deviation and pattern SD) were evaluated. The area under the receiver operating characteristic curve (AUROC) was calculated for each parameter to determine which best identified glaucomatous changes. RESULTS: Of the SD-OCT parameters, inferior (AUROC, 0.792) and mean GCC thickness (AUROC, 0.741) best discriminated between normal eyes and preperimetric glaucoma eyes. CONCLUSIONS: GCC measurements were more efficient than cpRNFL measurements in detecting preperimetric glaucomatous damage. This finding could be an aid to an early diagnosis.

Photopic negative response of full-field electroretinography in patients with different stages of glaucomatous optic neuropathy.

PURPOSE: To evaluate photopic negative response (PhNR) discrimination ability between healthy and glaucomatous patients. METHODS: Ninety eyes of 50 patients with primary open angle glaucoma (POAG) and 45 eyes of 23 healthy age- and sex-matched controls were investigated. Based on European Glaucoma Society criteria, POAG patients were divided into three groups: early, moderate and advanced glaucoma. Following measurements were analysed: mean defect (MD) from Humphrey Visual Field Analyzer, SITA standard 24-2 white on white perimetry; nerve fibre index (NFI) obtained from scanning laser polarimetry; and GDx and PhNR amplitude and PhNR/b-wave ratio. PhNR was elicited by red stimuli with flash strength of 1.6 cd s/m(2) on blue background of 25 cd/m(2). Correlations between retinal ganglion cells function (PhNR), retinal sensitivity (MD) and structure (NFI) were calculated. Sensitivity and specificity of PhNR parameters were calculated with standard formulas. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values. The area under the curve (AUC) was used to compare the ROC curves results between PhNR amplitude and ratio. RESULTS: PhNR amplitude and ratio were significantly reduced in early, moderate and advanced glaucoma groups compared to controls. The sensitivity and specificity to detect glaucoma in early POAG were equal to 53.3 and 90.0% for PhNR amplitude and 60.0 and 70.0% for PhNR ratio; in moderate POAG 63.3 and 80.0% for PhNR amplitude and 60.0 and 86.7% for PhNR ratio; and in advanced POAG 76.6 and 80.0% for PhNR amplitude, 90.0 and 73.3% for PhNR ratio. There were no significant differences between AUC for PhNR amplitude (0.76-0.86) and PhNR ratio (0.78-0.86), p > 0.05. PhNR amplitudes and ratios correlated significantly with MD measured by SAP and NFI obtained from GDx (p < 0.05). PhNR amplitude significantly decreases with advancement of visual field defects in glaucoma patients. CONCLUSIONS: PhNR reveals dysfunction of RGCs in early, moderate and advanced stage of POAG. PhNR has good discrimination ability in detecting glaucomatous patients. PhNR might be a useful test in glaucoma diagnosis.

Estimation of the Disc Damage Likelihood Scale in primary open-angle glaucoma: the Glaucoma Stereo Analysis Study.

PURPOSE: The Glaucoma Stereo Analysis Study (GSAS), a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We examined the associations between the Disc Damage Likelihood Scale (DDLS), a grading system for estimating glaucomatous ONH damage, and each parameter. METHODS: The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. ONH morphological parameters including the DDLS stage were calculated with prototype analysis software. Three independent graders classified each optic disc appearance into four different types: focal ischemic, myopic glaucomatous, senile sclerotic, and generalized enlargement. The correlations between the DDLS and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. RESULTS: The DDLS was correlated positively with baseline intraocular pressure and visual field pattern standard deviation, and negatively with visual field mean deviation. The DDLS was strongly correlated with vertical cup-to-disc ratio and horizontal cup-to-disc ratio positively, and with minimum rim-disc ratio negatively. The mean DDLS stage in the myopic glaucomatous type tended to be higher than the scores in other types. CONCLUSION: The DDLS obtained through three-dimensional ONH analysis correlates well with the severity of glaucomatous ONH and visual field damage.

Automated Detection of Glaucoma From Topographic Features of the Optic Nerve Head in Color Fundus Photographs.

OBJECTIVE: To describe and evaluate the performance of an automated CAD system for detection of glaucoma from color fundus photographs. DESIGN AND SETTING: Color fundus photographs of 2252 eyes from 1126 subjects were collected from 2 centers: Aravind Eye Hospital, Madurai and Coimbatore, India. The images of 1926 eyes (963 subjects) were used to train an automated image analysis-based system, which was developed to provide a decision on a given fundus image. A total of 163 subjects were clinically examined by 2 ophthalmologists independently and their diagnostic decisions were recorded. The consensus decision was defined to be the clinical reference (gold standard). Fundus images of eyes with disagreement in diagnosis were excluded from the study. The fundus images of the remaining 314 eyes (157 subjects) were presented to 4 graders and their diagnostic decisions on the same were collected. The performance of the system was evaluated on the 314 images, using the reference standard. The sensitivity and specificity of the system and 4 independent graders were determined against the clinical reference standard. RESULTS: The system achieved an area under receiver operating characteristic curve of 0.792 with a sensitivity of 0.716 and specificity of 0.717 at a selected threshold for the detection of glaucoma. The agreement with the clinical reference standard as determined by Cohen κ is 0.45 for the proposed system. This is comparable to that of the image-based decisions of 4 ophthalmologists. CONCLUSIONS AND RELEVANCE: An automated system was presented for glaucoma detection from color fundus photographs. The overall evaluation results indicated that the presented system was comparable in performance to glaucoma classification by a manual grader solely based on fundus image examination.

Characteristic correlations of the structure-function relationship in different glaucomatous disc types.

PURPOSE: To investigate the influence of the optic disc type on the overall and regional correlation between structure and function in open angle glaucoma (OAG). METHODS: We divided 144 eyes of 144 patients with OAG into four groups according to Nicolela et al.'s classification of optic disc type: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized enlargement (GE). We measured the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) with the 3D OCT-2000 and the mean deviation (MD) with the Humphrey Field Analyzer in each group and determined the influence of the disc type on these parameters with the Spearman rank correlation. RESULTS: We found that cpRNFLT and MD were significantly correlated in the MY (r = 0.61, P < 0.001), GE (r = 0.62, P < 0.001), and SS groups (r = 0.52, P = 0.002), but not in the FI group (r = 0.25, P = 0.130). The region of the optic disc with the highest correlation coefficient between structure and function differed according to the disc type. CONCLUSIONS: The correlation between cpRNFLT and MD varied according to the optic disc morphology in OAG. This suggests that different disc types have characteristic regional variations in the correlation between structure and function. The disc type should therefore be considered in investigations of the correlation between structure and function in glaucoma.

Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma.

PURPOSE: To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 104 healthy eyes of 104 normal participants. METHODS: All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. MAIN OUTCOME MEASURES: (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. RESULTS: Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). CONCLUSIONS: Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings.

A hierarchical cluster analysis of normal-tension glaucoma using spectral-domain optical coherence tomography parameters.

PURPOSE: Normal-tension glaucoma (NTG) is a heterogenous disease, and there is still controversy about subclassifications of this disorder. On the basis of spectral-domain optical coherence tomography (SD-OCT), we subdivided NTG with hierarchical cluster analysis using optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thicknesses. PATIENTS AND METHODS: A total of 200 eyes of 200 NTG patients between March 2011 and June 2012 underwent SD-OCT scans to measure ONH parameters and RNFL thicknesses. We classified NTG into homogenous subgroups based on these variables using a hierarchical cluster analysis, and compared clusters to evaluate diverse NTG characteristics. RESULTS: Three clusters were found after hierarchical cluster analysis. Cluster 1 (62 eyes) had the thickest RNFL and widest rim area, and showed early glaucoma features. Cluster 2 (60 eyes) was characterized by the largest cup/disc ratio and cup volume, and showed advanced glaucomatous damage. Cluster 3 (78 eyes) had small disc areas in SD-OCT and were comprised of patients with significantly younger age, longer axial length, and greater myopia than the other 2 groups. CONCLUSIONS: A hierarchical cluster analysis of SD-OCT scans divided NTG patients into 3 groups based upon ONH parameters and RNFL thicknesses. It is anticipated that the small disc area group comprised of younger and more myopic patients may show unique features unlike the other 2 groups.

Agreement among graders on Heidelberg retina tomograph (HRT) topographic change analysis (TCA) glaucoma progression interpretation.

PURPOSE: To evaluate agreement among experts of Heidelberg retina tomography's (HRT) topographic change analysis (TCA) printout interpretations of glaucoma progression and explore methods for improving agreement. METHODS: 109 eyes of glaucoma, glaucoma suspect and healthy subjects with ≥5 visits and 2 good quality HRT scans acquired at each visit were enrolled. TCA printouts were graded as progression or non-progression. Each grader was presented with 2 sets of tests: a randomly selected single test from each visit and both tests from each visit. Furthermore, the TCA printouts were classified with grader's individual criteria and with predefined criteria (reproducible changes within the optic nerve head, disregarding changes along blood vessels or at steep rim locations and signs of image distortion). Agreement among graders was modelled using common latent factor measurement error structural equation models for ordinal data. RESULTS: Assessment of two scans per visit without using the predefined criteria reduced overall agreement, as indicated by a reduction in the slope, reflecting the correlation with the common factor, for all graders with no effect on reducing the range of the intercepts between the graders. Using the predefined criteria improved grader agreement, as indicated by the narrower range of intercepts among the graders compared with assessment using individual grader's criteria. CONCLUSIONS: A simple set of predefined common criteria improves agreement between graders in assessing TCA progression. The inclusion of additional scans from each visit does not improve the agreement. We, therefore, recommend setting standardised criteria for TCA progression evaluation.

Novel use of 3T MRI in assessment of optic nerve volume in glaucoma.

PURPOSE: To measure optic nerve (ON) volume using 3 T magnetic resonance imaging (MRI), to correlate ON volume with retinal nerve fiber layer (RNFL) thickness, and to determine the viability of MRI as an objective tool in distinguishing glaucoma severity. METHODS: In this cross-sectional study, 30 severe glaucoma patients, 30 mild glaucoma patients and 30 age-matched controls were recruited. All subjects underwent standard automated perimetry, RNFL analysis and 3 T MRI examinations. Glaucoma patients were classified according to the Hodapp-Anderson-Parish classification. Pearson's correlation coefficient was used to correlate ON volume with RNFL, and receiver operating curve (ROC) analysis was performed to determine the sensitivity and specificity of ON volume in detecting glaucoma severity. RESULTS: Optic nerve volume was significantly lower in both the left and right eyes of the severe glaucoma group (168.70 ± 46.28 mm(3); 167.40 ± 45.36 mm(3)) than in the mild glaucoma group (264.03 ± 78.53 mm(3); 264.76 ± 78.88 mm(3)) and the control group (297.80 ± 71.45 mm(3); 296.56 ± 71.02 mm(3)). Moderate correlation was observed between: RNFL thickness and ON volume (r = 0.51, p <0.001), and in mean deviation of visual field and optic nerve volume (r = 0.60, p < 0.001). ON volume below 236 mm(3) was 96 % sensitive and 80 % specific for the detection of severe glaucoma. CONCLUSIONS: MRI measured optic nerve volume is a reliable method of assessing glaucomatous damage beyond the optic nerve head. A value of 236 mm(3) and below can be used to define severe glaucoma.

Variations of retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness according to the torsion direction of optic disc.

PURPOSE: To examine the relationship between the optic disc torsion and peripapillary retinal nerve fiber layer (RNFL) thickness through a comparison with the macular ganglion cell inner plexiform layer complex (GCIPL) thickness measured by Cirrus optical coherence tomography (OCT). METHODS: Ninety-four eyes of 94 subjects with optic disc torsion and 114 eyes of 114 subjects without optic disc torsion were enrolled prospectively. The participants underwent fundus photography and OCT imaging in peripapillary RNFL mode and macular GCIPL mode. The participants were divided into groups according to the presence or absence of optic disc torsion. The eyes with optic disc torsion were further divided into supranasal torsion and inferotemporal torsion groups according to the direction of optic disc torsion. The mean RNFL and GCIPL thicknesses for the quadrants and subsectors were compared. The superior and inferior peak locations of the RNFL were also measured according to the torsion direction. RESULTS: The temporal RNFL thickness was significantly thicker in inferotemporal torsion, whereas the GCIPL thickness at all segments was unaffected. The inferotemporal optic torsion had more temporally positioned superior peak locations of the RNFL than the nontorsion and supranasal-torted optic disc. CONCLUSIONS: Thickening of the temporal RNFL with a temporal shift in the superior peak within the eyes with inferotemporal optic disc torsion can lead to interpretation errors. The ganglion cell analysis algorithm can assist in differentiating eyes with optic disc torsion.

The relationship between cup-to-disc ratio and estimated number of retinal ganglion cells.

PURPOSE: To investigate the relationship between cup-to-disc ratio (CDR) and estimates of retinal ganglion cell (RGC) number. METHODS: This cross-sectional study included 156 healthy eyes, 53 glaucoma suspects, and 127 eyes with glaucoma. All eyes had standard automated perimetry (SAP), Cirrus SD-OCT, and stereoscopic optic disc photography within 6 months. CDR was determined from stereoscopic photographs by two or more masked graders. The number of RGCs in each eye was estimated using a published model that combines estimates of RGC number from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer measurements. RESULTS: The mean estimated RGC count was 1,063,809 in healthy eyes; 828,522 in eyes with suspected glaucoma; and 774,200 in early, 468,568 in moderate, and 218,471 in advanced glaucoma. Healthy eyes had a mean vertical CDR of 0.45 ± 0.15 vs. 0.80 ± 0.16 in glaucomatous eyes. There was good correlation between stereophotographic vertical CDR and SD-OCT vertical CDR (R(2) = 0.825; P < 0.001). The relationship between estimated RGCs and vertical CDR was best represented using a third degree polynomial regression model, including age and optic disc area, which accounted for 83.3% of the variation in estimated RGC counts. The nonlinear relationship between RGC estimates and CDRs indicated that eyes with a large CDR would require loss of large RGC numbers for a small increase in CDR. CONCLUSIONS: The relationship between estimated RGC counts and CDR suggests that assessment of change in CDR is an insensitive method for evaluation of progressive neural losses in glaucoma. Even relatively small changes in CDR may be associated with large losses of RGCs, especially in eyes with large CDRs. (ClinicalTrials.gov numbers, NCT00221923, NCT00221897.).

Validity of a new optic disc grading software for use in clinical and epidemiological research.

BACKGROUND: To determine the reliability and agreement of a new optic disc grading software program for use in clinical, epidemiological research. DESIGN: Reliability and agreement study. SAMPLES: 328 monoscopic and 85 stereoscopic optic disc images. METHODS: Optic disc parameters were measured using a new optic disc grading software (Singapore Optic Disc Assessment) that is based on polynomial curve-fitting algorithm. Two graders independently graded 328 monoscopic images to determine intergrader reliability. One grader regraded the images after 1 month to determine intragrader reliability. In addition, 85 stereo optic disc images were separately selected, and vertical cup-to-disc ratios were measured using both the new software and standardized Wisconsin manual stereo-grading method by the same grader 1 month apart. Intraclass correlation coefficient (ICC) and Bland-Altman plot analyses were performed. MAIN OUTCOME MEASURES: Optic disc parameters. RESULTS: The intragrader and intergrader reliability for optic disc measurements using Singapore Optic Disc Assessment was high (ICC ranging from 0.82 to 0.94). The mean differences (95% limits of agreement) for intergrader vertical cup-to-disc ratio measurements were 0.00 (-0.12 to 0.13) and 0.03 (-0.15 to 0.09), respectively. The vertical cup-to-disc ratio agreement between the software and Wisconsin grading method was extremely close (ICC = 0.94). The mean difference (95% limits of agreement) of vertical cup-to-disc ratio measurement between the two methods was 0.03 (-0.09 to 0.16). CONCLUSIONS: Intragrader and intergrader reliability using Singapore Optic Disc Assessment was excellent. This software was highly comparable with standardized stereo-grading method. Singapore Optic Disc Assessment is useful for grading digital optic disc images in clinical, population-based studies.