Circumpapillary Retinal Nerve Fiber Layer Research Articles

Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma.

To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: β=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: β=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: β=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: β=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

Anatomical Features can Affect OCT Measures Used for Clinical Decisions and Clinical Trial Endpoints.

To understand the association between anatomical parameters of healthy eyes and optical coherence tomography (OCT) circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. OCT cpRNFL thickness was obtained from 396 healthy eyes in a commercial reference database (RDB). The temporal quadrant (TQ), superior quadrant (SQ), inferior quadrant (IQ), and global (G) cpRNFL thicknesses were analyzed. The commercial OCT devices code these values based on percentiles (red, <1%; yellow, ≥1% and <5%), after taking age and disc area into consideration. Four anatomical parameters were assessed: fovea-to-disc distance, an estimate of axial length, and the locations of the superior and the inferior peaks of the cpRNFL thickness curve. Pearson correlation values were obtained for the parameters and the thickness measures of each of the four cpRNFL regions, and t-tests were performed between the cpRNFL thicknesses coded as abnormal (red or yellow, <5%) versus normal (≥5%). For each of the four anatomical parameters, the correlation with the thickness of one or more of the TQ, SQ, IQ, and G regions exceeded the correlation with age or disc area. All four parameters were significantly (P < 0.001) associated with the abnormal cpRNFL values. The significant parameters were not the same for the different regions; for example, a parameter could be negatively correlated for the TQ but positively correlated with the SQ or IQ. In addition to age and disc area, which are used for inferences in normative databases, four anatomical parameters are associated with cpRNFL thickness. Taking these additional anatomical parameters into consideration should aid diagnostic accuracy.

Evaluation of Optic Nerve Head Microcirculation in Open-Angle Glaucoma Patients with Unilateral Visual Field Defect.

Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.

Intraocular pressure‐related side‐effects after endothelial keratoplasty

AbstractPurposeTo investigate circumpapillary retinal nerve fibre layer (RNFL) thickness, pupillary function and diameter after phacoemulsification and lens implantation alone or combined with endothelial keratoplasty (EK).MethodsThis study was a secondary analysis of data from a randomized, single‐masked trial, that included 72 patients with Fuchs' endothelial dystrophy and cataract, equally allocated (1:1) to ultrathin Descemet's stripping automated endothelial keratoplasty or Descemet's membrane endothelial keratoplasty. The cataract extraction (CE) group included 40 patients undergoing cataract surgery only. All patients were treated with phacoemulsification and lens implantation.ResultsRNFL thickness was significantly lower in the CE group than after EK for the global (p &lt; 0.01), nasal (p = 0.04), and temporal sectors (p = 0.01) 12 months after surgery. RNFL thickness was comparable between patients treated with rebubbling and others (p ≥ 0.16 for all comparisons) after 12 months. The CE group and patients treated with EK demonstrated a comparable scotopic (p = 0.34) and photopic pupil diameter (p = 0.95) as well as a comparable maximum (p = 0.83) and average pupillary constriction velocity (p = 0.95) after 12 months. In contrast, patients treated with rebubbling had a significantly smaller scotopic pupil diameter (p = 0.04).ConclusionIn this study, no evidence was found indicating a negative impact on the RNFL thickness after EK when compared to CE 12 months after surgery. Iris function and pupil diameter were comparable between the CE group and patients treated with EK after 12 months.

Visual Field Deficits in Albinism in Comparison to Idiopathic Infantile Nystagmus.

This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA. VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region. Mean detection thresholds were significantly lower than normative values for PwA (-3.10 ± 1.67 dB, P << 0.0001) and PwIIN (-1.70 ± 1.54 dB, P<0.0001). Mean detection thresholds were significantly lower in PwA compared to PwIIN (P<0.0001) and significantly worse for left compared to right eyes in PwA (P=0.0002) but not in PwIIN (P=0.37). In PwA, the superior nasal VF was significantly worse than other quadrants (P<0.05). PwIIN appeared to show a mild relative arcuate scotoma. In PwA, central detection thresholds were correlated with foveal changes in the inner and outer retina. VF was strongly correlated to BCVA in both groups. Clear peripheral and central VF deficits exist in PwA and PwIIN, and static VF results need to be interpreted with caution clinically. Since PwA exhibit considerably lower detection thresholds compared to PwIIN, VF defects are unlikely to be due to nystagmus in PwA. In addition to horizontal VF asymmetry, PwA exhibit both vertical and interocular asymmetries, which needs further exploration.

Optical coherence tomography in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence tomography (OCT) have recently been identified as a potential biomarker for this disease. We aimed to measure circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using OCT and to compare the results in healthy participants with those of individuals having clinically definitive MS with and without a history of optic neuritis. This cross-sectional study recruited patients with clinically confirmed MS, with and without optic neuritis, and healthy individuals as a control group. We documented demographic characteristics, duration of MS, and time elapsed since the episode of optic neuritis. All participants underwent a thorough ocular examination and measurement of total, superior, and inferior cpRNFLT using swept-source OCT. In participants with MS, women outnumbered men in the subsets with (90%) and without (64%) optic neuritis. The control group comprised approximately similar numbers of men and women. There was a statistically significant difference in total, superior, and inferior cpRNFLT between study groups (all P < 0.001). Pairwise comparisons revealed significantly thinner total, superior, and inferior cpRNFLTs in patients having MS with and without (all P < 0.001) optic neuritis when compared with the controls. We found significantly higher total, superior, and inferior cpRNFLTs in women than in men (all P < 0.05). However, we found no significant correlation between total, superior, or inferior cpRNFLT and patient age, duration of MS, or time elapsed since the optic neuritis episode (all P > 0.05), except for a significant moderate inverse correlation between patient age and total cpRNFLT (r = - 0.41; P < 0.05), indicating a loss of total cpRNFLT with age. Patients with clinically confirmed MS, with or without optic neuritis, had a significantly decreased cpRNFLT compared to that of healthy individuals. There was a significant inverse correlation between age and total cpRNFLT and a difference in cpRNFLT between the sexes, indicating that age and sex may influence the measurement of cpRNFLT using OCT in patients with MS. As a screening tool, OCT should be used along with other existing diagnostic modalities for patients with definite or suspected MS. Further longitudinal studies including various classifications of MS with or without isolated episodes of optic neuritis, along with diagnostic accuracy studies, could provide more robust conclusions on the suitability of OCT as a biomarker of MS.

Comparison of the Circumpapillary Structure-Function and Vasculature-Function Relationships at Different Glaucoma Stages Using Longitudinal Data.

This study investigated the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) data using circumpapillary retinal nerve fiber layer thickness (cpRNFLT) measurements from optical coherence tomography (OCT), circumpapillary vessel density (cpVD) from OCT angiography (OCTA), and the corresponding visual field mean sensitivities at different glaucoma stages. A total of 107 eyes from 107 glaucoma patients with progressive visual field (VF) changes followed up for an average of 3.33 ± 1.39years were enrolled, including early-to-moderate (51 eyes) and advanced (56 eyes) stages. The rates of longitudinal change in the VF mean deviation (MD), cpRNFLT, and cpVD were evaluated using linear mixed-effects models and compared between different glaucoma stages. Longitudinal global and regional S-F and V-F relationships were assessed by repeated measures correlation analysis by glaucoma stage. No significant differences were found in the rates of VF MD and cpVD changes (P > 0.05) between the two glaucoma stage groups. CpRNFLT decreased more rapidly in the early-to-moderate stage group (P < 0.001) in which significant longitudinal global and regional correlations were found in both S-F and V-F relationships (all P < 0.05), except for the nasal sector. Significant global and regional correlations were only found in V-F relationship in advanced stage cases (all P < 0.05). Significant longitudinal V-F relationships exist globally and regionally regardless of glaucoma stage but no longitudinal S-F relationship is present in advanced glaucoma. Longitudinal follow-up of cpVD parameters may be useful for monitoring glaucomatous VF progression at all disease stages.

Which OCT Measure of the Optic Nerve Head Improves Fastest? Towards Optimizing Early Detection of Resolving Papilledema in Children.

Optical coherence tomography (OCT) has been used to monitor papilledema. This study aims to determine which OCT-derived measures of the optic nerve head (ONH) detect resolving papilledema in children faster than standard OCT measures. Children (≤18years of age) with papilledema who completed optic nerve SD-OCT pretreatment and had evidence of treatment response on one or more follow-up OCTs within 4months were included. Standard (mean circumpapillary retinal nerve fiber layer [cpRNFL] thickness), device-derived (per-quadrant cpRNFL) and custom (ONH height, maximum Bruch's membrane displacement [BMD], ONH volume [ONHV], and BMD volume) OCT measures were calculated. Per-eye generalized estimating equations (GEEs) modelled changes in device-derived and custom measures as a function of mean cpRNFL to identify those measures that resolved faster during early (0-2months) follow-up. Mean cpRNFL coefficients of greater than 1 indicated faster resolving papilledema. We included 52 eyes of 29 children (mean age, 12.8years; 72.4% female). In analysis of early follow-up visits (38 eyes from 22 children), nasal cpRNFL and maximum BMD in each quadrant resolved faster than mean cpRNFL (GEE coefficients range, 1.14-3.37). Inferior cpRNFL, superior, nasal, and inferior ONH heights and ONHV resolved slower than mean cpRNFL (GEE coefficients range, 0.67-0.87). Nasal cpRNFL is a promising device-derived OCT measure for the early detection of resolving papilledema in children compared with mean cpRNFL. Maximum BMD, a custom measure, also shows promise, but its calculation has not yet been incorporated into commercial OCT devices. This study guides the optimal use of OCT in capturing resolving papilledema in children.

Morphological and vascular evidence of glaucomatous damage in myopic guinea pigs with scleral crosslinking

Guinea pigs are often used as models for myopia studies. However, the imaging structure and vasculature of the optic nerve head (ONH) in guinea pigs are tentative. This study investigated morphological parameters and vascular characteristics of the ONH in guinea pigs with form deprivation (FD) myopia before and after scleral crosslinking (CXL), using optical coherence tomography (OCT) and OCT angiography (OCTA). Refractive error, axial length (AL), intraocular pressure (IOP), and OCT-based structural parameters of the ONH were measured at baseline and 3 weeks after the FD + CXL procedure in guinea pigs. The 88 guinea pigs analysed in this study were aged 3 (n = 29), 4 (n = 51), and 5 (n = 8) weeks. The IOP, AL, average and vertical cup-to-disc ratio (C/D), circumpapillary retinal nerve fibre layer, disc area, and cup volume increased at 3 weeks compared to baseline values (all p < 0.001). The refractive error and rim area decreased at 3 weeks compared to baseline values (all p < 0.001). After adjustment for age, IOP was correlated positively with average C/D (p = 0.039) and negatively with rim area (p = 0.009). The severity of blood signal defects was positively associated with the average C/D at 3 weeks (p = 0.027). These findings may facilitate further research on myopia using guinea pigs.

Evaluating the diagnostic performance with neurovascular segregation of the retinal nerve fibre layer in glaucoma

Aims/Purpose: To evaluate the diagnostic performance in detecting eyes with glaucoma by segregating the neuronal and vascular components in circumpapillary optical coherence tomography (OCT) and OCT angiography (OCTA) scans.Methods: In this study, 93 participants with glaucoma were age‐ and gender‐matched with normal controls with no ocular diseases. OCT and OCTA volumetric images of one eye from each participant were acquired using a prototype high resolution swept source OCT imaging system (Zeiss PlexElite) using a 6 mm x 6 mm imaging protocol centered at the optic nerve head. Circumpapillary OCT and OCTA images with a diameter of 3.46 mm were subsequently generated. Information from the circumpapillary and enface OCTA images were used to isolate and segregate the vascular components from the circumpapillary retinal nerve fibre layer (RNFL), which was obtained using a deep learning segmentation approach. Thicknesses of the RNFL with and without the vascular components were measured and diagnostic performance was evaluated using area under the receiving operating characteristic curve (AUC) analysis. Both global and quadrant (superior, inferior, nasal and temporal) measurements around the optic nerve head were considered.Results: Imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired. Using only the global RNFL thickness, the detection of glaucoma achieved an AUC of 0.877 ± 0.021. With the vascular components excluded from the global RNFL thickness, an AUC of 0.890 ± 0.020 was obtained. When the vascular and non‐vascular components of the RNFL in the different quadrants were modelled separately, AUC improved to 0.927 ± 0.015, and was found to be significantly higher than the detection of glaucoma using global measures (p &lt; 0.001).Conclusions: Segregation of vascular and non‐vascular components in the retinal nerve fibre layer led to an improvement in glaucoma detection. Further improvements were observed when the contributions of the components in the RNFL quadrants were modelled separately.

Comparison of the TEMPO binocular perimeter and Humphrey field analyzer

This study compared between TEMPO, a new binocular perimeter, with the Humphrey Field Analyzer (HFA). Patients were tested with both TEMPO 24–2 Ambient Interactive Zippy Estimated by Sequential Testing (AIZE)-Rapid and HFA 24–2 Swedish Interactive Threshold Algorithm (SITA)-Fast in a randomized sequence on the same day. Using a mixed-effects model, visual field (VF) parameters and reliability indices were compared. Retinal nerve fiber layer (RNFL) thickness was measured using Cirrus optical coherence tomography (OCT), and coefficient of determinations for VF and OCT parameters were calculated and compared using Akaike information criteria. 740 eyes (including 68 healthy, 262 glaucoma suspects, and 410 glaucoma) of 370 participants were evaluated. No significant differences were seen in mean deviation and visual field index between the two perimeters (P > 0.05). A stronger association between VF mean sensitivity (dB or 1/L) and circumpapillary RNFL was found for TEMPO (adjusted R2 = 0.25; Akaike information criteria [AIC] = 5235.5 for dB, and adjusted R2 = 0.29; AIC = 5200.8 for 1/L, respectively) compared to HFA (adjusted R2 = 0.22; AIC = 5263.9 for dB, and adjusted R2 = 0.22; AIC = 5262.7 for 1/L, respectively). Measurement time was faster for TEMPO compared to HFA (261 s vs. 429 s, P < 0.001). Further investigations are needed to assess the long-term monitoring potential of this binocular VF test.

Abilities of circumpapillary retinal nerve fiber layer thickness and vascular density to discriminate stages in primary open-angle glaucoma.

To clarify the abilities of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) obtained by optical coherence tomography (OCT) and circumpapillary vessel density (cpVD) measured by OCT-angiography to distinguish different stages in primary open-angle glaucoma determined by 24-2 or 30-2 static visual field (VF) testing. This retrospective study includes 25 healthy normal eyes of 25 subjects and 87 primary open-angle glaucoma eyes of 87 patients. Areas under the receiver operating characteristic curves (AUROC) were evaluated for determining glaucoma stages using cpRNFLT and cpVD. The absolute errors of the estimated mean total deviation (mTD) using optimal models with cpRNFLT and cpVD were also compared. The AUROCs for discriminating glaucomatous eyes from normal eyes was significantly higher for cpRNFLT than the respective AUROCs for cpVD (0.969 [95% CI 0.939 to 0.998] vs. 0.872 [95% CI 0.806 to 0.938], p = 0.006), whereas cpVD had significantly higher AUROC for discriminating severe glaucoma eyes from moderate glaucoma eyes than cpRNFLT (0.771 [95% CI 0.655 to 0.886] vs. 0.578 [95% CI 0.420 to 0.736], p = 0.022). The mean absolute error in estimating mTD using both cpRNFLT and cpVD was significantly less than the error using cpRNFLT alone (4.56 ± 3.76dB vs. 5.39 ± 4.00dB, p = 0.027). Our results suggest that cpVD is better for follow-ups after moderate stage. The combination of cpRNFLT and cpVD may improve VF estimation compared to cpRNFLT alone.

Normative Percentiles of Retinal Nerve Fiber Layer Thickness and Glaucomatous Visual Field Loss.

Circumpapillary 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. A 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. There 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. Our 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. Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

Predictive potential of optical coherence tomography parameters for the prognosis of decreased visual acuity after trabeculectomy in open-angle glaucoma patients with good vision

BackgroundTrabeculectomy (trab) is the most effective surgical procedure for lowering IOP and preventing glaucoma progression. However, decline in best-corrected visual acuity (BCVA) is one of the most serious postoperative complications of trab. Here, we investigated methods to predict decreased BCVA after trab in glaucoma patients with good preoperative BCVA.MethodsThis study included 35 eyes of 35 open-angle glaucoma (OAG) patients (male / female: 21 / 14, age: 64.0 ± 9.7 years old, preoperative intraocular pressure: 15.9 ± 5.4 mmHg, mean deviation: -18.1 ± 5.6 dB) with preoperative BCVA of 0.7 or better who underwent trab and were observed for more than 12 months. As a preoperative analysis, we measured temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell complex thickness in a central strip between the disc and fovea (csGCCT), an area that corresponds to the location of the papillomacular bundle (PMB) in swept-source optical coherence tomography (OCT). We defined BCVA decline as a loss of more than 3 lines of BCVA after 12 months. Measurement parameters were compared between the BCVA-decline group and the non-BCVA-decline group.ResultsBCVA decline was detected in 11 cases (31.4%) 12 months after trab. There was a statistically significant difference in axial length (P = 0.049). A single logistic analysis showed that the BCVA-decline group had significantly lower cpRNFLT than the non-BCVA-decline group (27.7 ± 8.0 μm vs. 45.1 ± 5.3 μm, P < 0.001, cut-off value: 33.4 μm), as well as lower csGCCT (72.4 ± 7.7 μm vs. 87.5 ± 5.1 μm, P = 0.002, cut-off value: 82.3 μm). Multivariable logistic analysis showed that the BCVA-decline group had significantly lower temporal quadrant cpRNFLT (P < 0.001) and lower middle csGCCT (P < 0.001) compared to the non-BCVA-decline group.ConclusionsLower temporal quadrant cpRNFLT and middle csGCCT, OCT scan areas that correspond to the location of the PMB, might be biomarkers that predict BCVA decline after trab in OAG patients with good vision.

Extracting decision-making features from the unstructured eye movements of clinicians on glaucoma OCT reports and developing AI models to classify expertise.

This study aimed to investigate the eye movement patterns of ophthalmologists with varying expertise levels during the assessment of optical coherence tomography (OCT) reports for glaucoma detection. Objectives included evaluating eye gaze metrics and patterns as a function of ophthalmic education, deriving novel features from eye-tracking, and developing binary classification models for disease detection and expertise differentiation. Thirteen ophthalmology residents, fellows, and clinicians specializing in glaucoma participated in the study. Junior residents had less than 1 year of experience, while senior residents had 2-3 years of experience. The expert group consisted of fellows and faculty with over 3 to 30+ years of experience. Each participant was presented with a set of 20 Topcon OCT reports (10 healthy and 10 glaucomatous) and was asked to determine the presence or absence of glaucoma and rate their confidence of diagnosis. The eye movements of each participant were recorded as they diagnosed the reports using a Pupil Labs Core eye tracker. Expert ophthalmologists exhibited more refined and focused eye fixations, particularly on specific regions of the OCT reports, such as the retinal nerve fiber layer (RNFL) probability map and circumpapillary RNFL b-scan. The binary classification models developed using the derived features demonstrated high accuracy up to 94.0% in differentiating between expert and novice clinicians. The derived features and trained binary classification models hold promise for improving the accuracy of glaucoma detection and distinguishing between expert and novice ophthalmologists. These findings have implications for enhancing ophthalmic education and for the development of effective diagnostic tools.

Agreement and precision of wide and cube scan measurements between swept-source and spectral-domain OCT in normal and glaucoma eyes

This study aimed to evaluate agreement of Wide scan measurements from swept-source optical coherence tomography (SS-OCT) Triton and spectral-domain OCT (SD-OCT) Maestro in normal/glaucoma eyes, and to assess the precision of measurements from Wide and Cube scans of both devices. Three Triton and three Maestro operator/device configurations were created by pairing three operators, with study eye and testing order randomized. Three scans were captured for Wide (12 mm × 9 mm), Macular Cube (7 mm × 7 mm–Triton; 6 mm × 6 mm-Maestro), and Optic Disc Cube (6 mm × 6 mm) scans for 25 normal eyes and 25 glaucoma eyes. Parameter measurements included circumpapillary retinal nerve fiber layer(cpRNFL), ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++). A two-way random effect analysis of variance model was used to estimate the repeatability and reproducibility; agreement was evaluated by Bland–Altman analysis and Deming regression. The precision estimates were low, indicating high precision, for all thickness measurements with the majority of the limits < 5 µm for the macula and < 10 µm for the optic disc. Precision of the Wide and Cube scans were comparable. Excellent agreement between the two devices was found for Wide scans, with the mean difference < 3 µm across all measurements (cpRNFL < 3 µm, GCL+ < 2 µm, GCL ++ < 1 µm), indicating interoperability. A single Wide scan covering the peripapillary and macular regions may be useful for glaucoma diagnosis and management.

Larger Tumor Volume is Associated with Visual Acuity Loss and Axonal Degeneration in Children with Optic Pathway Gliomas Secondary to Neurofibromatosis Type 1

Abstract BACKGROUND We investigated whether volumetric magnetic resonance imaging (MRI) measures of the anterior visual pathway (AVP) in optic pathway gliomas secondary to Neurofibromatosis type 1 (NF1-OPG) are associated with visual acuity (VA) loss and axonal loss, as measured using optical coherence tomography (OCT). METHODS Children with NF1-OPGs enrolled in a prospective study of VA and OCT measures of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness were eligible if they had undergone 3-Tesla MRI that included a T1-weighted volumetric sequence. The linear dimension and volume of the optic nerves, chiasm and optic tracts were measured using our semi-automated algorithm. The combined volume of these components comprising the proximal AVP was used as a surrogate of total tumor burden. Regression models for VA and cpRNFL thickness were reported on a per-eye basis. RESULTS Fifty-two study eyes (26 children, mean 7.1 years) met inclusion criteria, of which 40% (N=21 eyes) had abnormal VA. In regression analysis, only total AVP volume demonstrated a significant relationship to axonal loss, such that for every 1 ml increase in AVP volume, cpRNFL declined by 5.4 microns (p = 0.01). Total AVP volume &amp;gt; 1.75 ml predicted both axonal loss and abnormal VA (positive predictive value of 83.3% and 70.8%, respectively; negative predictive value of 80.0% and 88.0%, respectively). CONCLUSIONS Volumetric measures of NF1-OPGs identified children with VA loss and axonal degeneration. Total tumor burden, as measured by AVP volume, had the strongest relationship with axonal injury. NF1-OPG volumetric measures may be helpful in making treatment decisions.

An Artificial Intelligence Enabled System for Retinal Nerve Fiber Layer Thickness Damage Severity Staging

To develop an objective glaucoma damage severity classification system based on OCT-derived retinal nerve fiber layer (RNFL) thickness measurements. Algorithm development for RNFL damage severity classification based on multicenter OCT data. A total of 6561 circumpapillary RNFL profiles from 2269 eyes of 1171 subjects to develop models, and 2505 RNFL profiles from 1099 eyes of 900 subjects to validate models. We developed an unsupervised k-means model to identify clusters of eyes with similar RNFL thickness profiles. We annotated the clusters based on their respective global RNFL thickness. We computed the optimal global RNFL thickness thresholds that discriminated different severity levels based on Bayes' minimum error principle. We validated the proposed pipeline based on an independent validation dataset with 2505 RNFL profiles from 1099 eyes of 900 subjects. Accuracy, area under the receiver operating characteristic curve, and confusion matrix. The k-means clustering discovered 4 clusters with 1382, 1613, 1727, and 1839 samples with mean (standard deviation) global RNFL thickness of 58.3 (8.9) μm, 78.9 (6.7) μm, 87.7 (8.2) μm, and 101.5 (7.9) μm. The Bayes' minimum error classifier identified optimal global RNFL values of > 95 , 86 to 95 , 70 to 85 and < 70 for discriminating normal eyes and eyes at the early, moderate, and advanced stages of RNFL thickness loss, respectively. About 4% of normal eyes and 98% of eyes with advanced RNFL loss had either global, or ≥ 1 quadrant, RNFL thickness outside of normal limits provided by the OCT instrument. Unsupervised machine learning discovered that the optimal RNFL thresholds for separating normal eyes and eyes with early, moderate, and advanced RNFL loss were 95 , 85 μm, and 70 , respectively. This RNFL loss classification system is unbiased as there was no preassumption or human expert intervention in the development process. Additionally, it is objective, easy to use, and consistent, which may augment glaucoma research and day-to-day clinical practice. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neurovascular segregation of the retinal nerve fiber layer in glaucoma.

The imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired to evaluate the contributions of the neuronal and vascular components within the retinal nerve fiber layer (RNFL) for detecting glaucoma and modeling visual field loss through the use of optical coherence tomography (OCT) and OCT angiography. The neuronal and vascular components within the circumpapillary RNFL were independently evaluated. In healthy eyes, the neuronal component showed a stronger association with age (r = -0.52, p < 0.001) compared to measured RNFL thickness (r = -0.46, p < 0.001). Using the neuronal component alone improved detection of glaucoma (AUC: 0.890 ± 0.020) compared to measured RNFL thickness (AUC: 0.877 ± 0.021; χ2 = 5.54, p = 0.019). Inclusion of the capillary components with the sectoral neuronal component resulted in a significant improvement in glaucoma detection (AUC: 0.927 ± 0.015; χ2 = 15.34, p <0.001). After adjusting for potential confounders, AUC increased to 0.952 ± 0.011. Results from modeling visual field loss in glaucoma eyes suggest that visual field losses associated with neuronal thinning were moderated in eyes with a larger capillary component. These findings suggest that segregation of the neurovascular components could help improve understanding of disease pathophysiology and affect disease management in glaucoma.

Evaluation of inner retinal function at different stages of primary open angle glaucoma using the photopic negative response (PhNR) measured by RETeval electroretinography.

To investigate the objective function of the inner retinal layer in each stage of primary open angle glaucoma (POAG) using the photopic negative response (PhNR) measured by RETeval full-field electroretinography (ERG), and to identify which PhNR parameter is the most useful. Ninety eyes of 90 patients with POAG (30 with mild POAG (mean deviation (MD) ≥ -6dB) and 60 with moderate-to-advanced POAG (MD < -6dB)) and 76 eyes of 76 control cases were examined. We investigated six PhNR parameters and their relationships with the results of the Humphrey 30-2 visual field test and the thickness of the circumpapillary retinal nerve fiber layer (cpRNFL) obtained from optical coherence tomography. The following PhNR parameters were assessed: base-to-trough (BT), peak-to-trough (PT), 72msPhNR, the W-ratio, P-ratio, implicit time (IT), and a-wave and b-wave amplitudes on ERG. All PhNR parameters other than IT significantly differed between the all POAG (all stages) and control groups and between the moderate-to-advanced POAG and control groups. BT and 72msPhNR in the mild POAG group, significantly differed from those in the control group. Regarding the relationships between PhNR parameters and the visual field and between these parameters and cpRNFL thickness, correlations were observed between all PhNR parameters, except PT and IT, and both the visual field and cpRNFL thickness in the all and moderate-to-advanced POAG groups. 72msPhNR correlated with cpRNFL thickness in the mild POAG group. The area under the receiver operating characteristic curve was greater for BT than for the other PhNR parameters in both the mild and moderate-to-advanced POAG groups. The discriminant linear function for examining the presence or absence of POAG and the threshold for diagnosis were quantitatively obtained as follows. Regarding BT: discriminant = 0.505 × BT + 2.017; threshold = positive for POAG, negative for no POAG; correct answer rate = 80.7%. Concerning 72msPhNR: discriminant = 0.533 × 72msPhNR + 1.553; threshold = positive for POAG and negative for no POAG; correct answer rate = 77.1%. RETeval-measured PhNR parameters were useful for an objective evaluation of visual function in moderate-to-advanced POAG. BT appeared to be the most diagnostically useful parameter.