Retinal Nerve Fiber Layer Photography Research Articles

Deep-learning-based prediction of glaucoma conversion in normotensive glaucoma suspects

Background/aimsTo assess the performance of deep-learning (DL) models for prediction of conversion to normal-tension glaucoma (NTG) in normotensive glaucoma suspect (GS) patients.MethodsDatasets of 12 458 GS eyes were reviewed. Two...

Clinical usefulness of layer-by-layer deviation maps of Spectralis OCT: comparison with Cirrus OCT

Background/aimsTo compare the diagnostic abilities of Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Cirrus (Carl Zeiss Meditec, Dublin, California, USA) spectral domain–optical coherence tomography (OCT) for retinal nerve fibre layer (RNFL)...

The choroidal microvasculature of the parapapillary area as a biomarker of glaucoma development in the fellow eye of patients with unilateral glaucoma.

To investigate the factors associated with the development of glaucoma in the healthy eyes of unilateral glaucoma patients. This was a retrospective observational case series study. All participants had unilateral primary open-angle glaucoma at the initial visit and were divided into two groups: one in which the fellow eyes developed glaucoma during the follow-up period and one in which the fellow eyes remained healthy. A complete ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, intraocular pressure measurement, retinal nerve fiber layer and optic disk photographs, a 30-2 visual field test, and optical coherence tomography with angiography, was performed over a follow-up period of at least 3years. A total of fifty-six patients were enrolled, and over the course of the study period, 11 patients developed glaucoma in the fellow eyes, while the fellow eyes of 45 patients remained healthy. At the baseline, the glaucomatous eye had a larger area of beta parapapillary atrophy, lower parapapillary choroidal vascular density (pCVD) within the area, and a lower prevalence of microvascular dropout than normal fellow eyes (P < 0.001, 0.013, 0.001, respectively). In the multivariate analysis, a reduced pCVD in the gamma parapapillary atrophy (γPPA) region was significantly associated with the development of glaucoma in normal eyes (odds ratio, 0.566; 95% CI, 0.342, 0.935; P = 0.026). The pCVD within the γPPA region at baseline is the risk factor for the development of glaucoma in the normal fellow eye of patients with unilateral glaucoma.

Analysis of Variation in Incidence of Optic Disc Hemorrhage According to Seasonal and Temperature Changes

To investigate seasonal variation in optic disc hemorrhage (DH) by review of fundus photographs representative of 2 calendar years (2019 and 2020). Retrospective, observational trend study. Patients who visited the Glaucoma Clinic of Seoul National University Hospital and underwent fundus photography were included. All available stereo disc photographs and red-free retinal nerve fiber layer photographs taken between January 1, 2019 and December 31, 2020 were retrospectively reviewed. The monthly incidence rate of DH was determined by reference to the photographs. Seasonal temperature information and patients' intraocular pressure (IOP) information were obtained, organized, and analyzed. Fundus images of 13,514 eyes were reviewed, and 454 eyes were confirmed to have DH. Poisson regression analyses revealed that as the temperature (T) increased by 1 °C, the DH risk ratio was reduced to 0.979 (95% confidence interval [CI] 0.969-0.989, P < .01). The DH incidence ratio was 1.53 (95% CI 1.23-1.91, P < .01) for the T <10 °C group relative to the T ≥20 °C group. The IOP of the patients with DH in winter was significantly higher than that measured in summer. DH is affected by temperature, and as such, shows seasonal variability. This variability is believed to be caused by temperature-related factors such as IOP or hematological factors. © 2022 Elsevier Inc. All rights reserved.

Diagnostic assessment of glaucoma and non-glaucomatous optic neuropathies via optical texture analysis of the retinal nerve fibre layer.

The clinical diagnostic evaluation of optic neuropathies relies on the analysis of the thickness of the retinal nerve fibre layer (RNFL) by optical coherence tomography (OCT). However, false positives and false negatives in the detection of RNFL abnormalities are common. Here we show that an algorithm integrating measurements of RNFL thickness and reflectance from standard wide-field OCT scans can be used to uncover the trajectories and optical texture of individual axonal fibre bundles in the retina and to discern distinctive patterns of loss of axonal fibre bundles in glaucoma, compressive optic neuropathy, optic neuritis and non-arteritic anterior ischaemic optic neuropathy. Such optical texture analysis can detect focal RNFL defects in early optic neuropathy, as well as residual axonal fibre bundles in end-stage optic neuropathy that were indiscernible by conventional OCT analysis and by red-free RNFL photography. In a diagnostic-performance study, optical texture analysis of the RNFL outperformed conventional OCT in the detection of glaucoma, as defined by visual-field testing or red-free photography. Our findings show that optical texture analysis of the RNFL for the detection of optic neuropathies is highly sensitive and specific.

Multicolor Imaging for Detection of Retinal Nerve Fiber Layer Defect in Myopic Eyes With Glaucoma

To investigate the diagnostic performance of multicolor imaging for detection of retinal nerve fiber layer (RNFL) defects in myopic eyes with glaucoma. Comparative diagnostic analysis. A total of 150 myopic eyes of 138 patients (< -1.00 diopter or axial length >24 mm) underwent multicolor imaging by Spectralis (Heidelberg Engineering GmbH) optical coherence tomography (OCT). Two independent observers graded the RNFL visibility score and determined the location of the RNFL defect on each image. Readings were taken from the superior and inferior areas. The diagnostic performances of multicolor, green-reflectance, and blue-reflectance images for detection of the RNFL defect were compared with those of conventional fundus and red-free RNFL photographs. The interobserver agreement on the RNFL visibility score was substantial for fundus and RNFL photographs and multicolor and green-reflectance images and was perfect for blue-reflectance images. The interobserver agreement on the location of the RNFL defect was better when using multicolor imaging than when using conventional photography. The green-reflectance image (2.89 ± 0.31) showed the highest RNFL visibility score, followed by blue-reflectance (2.88 ± 0.32) and multicolor (2.57 ± 0.63) images. The sensitivity of multicolor imaging (94.9%, 93.2%, and 91.5% for green-reflectance, blue-reflectance, and multicolor images, respectively) was significantly higher than that of fundus photography (83.1%) for detection of superotemporal RNFL defects (all P < .05). It was significantly higher for inferotemporal defects than those of fundus and RNFL photographs (all P < .05). Multicolor imaging can visualize the glaucomatous RNFL defects in myopic eyes that are indistinguishable on conventional photography.

Combined structure–function analysis in glaucoma screening

AimTo assess the applicability of a structure–function (S-F) analysis combining spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP) in glaucoma screening in a middle-aged population.MethodsA randomised sample of...

Novel utilisation of ultrawide-field fundus photography for detecting retinal nerve fibre layer defects in glaucomatous eyes

Background/aimsEvaluation of the retinal nerve fibre layer (RNFL) is important for identifying glaucomatous damage. Ultrawide-field fundus photography (UWP) imaging is increasingly used in the ophthalmological field; however, it is unknown...

The severity of visual field defect and the defective angles of localized retinal nerve fiber layer using a novel approach

A modified novel analytical method for evaluating photographic retinal nerve fiber layer defect (RNFLD) was developed for the purpose of estimating the severity of early glaucomatous eyes. This new method was then compared with the original method, as described below, in relation to the visual field defect severity. The clinical records of 47 glaucomatous eyes with qualified photographs were obtained from a prior retrospective study. The reference point of the angle was set at the center of the optic disc center (COD group) and the central vessel trunk (COV group). Angle α was the angular width between the fovea and the proximity of RNFLD, while angle β (+c) was the sum of the angular width(s) of localized RNFLD. The correlation between the visual field parameters and the angles of RNFLD in the above two groups were analyzed. There were significant differences in angle α (p=0.001) and angle β (+c) (p=0.016) between the two groups. Angle β (+c) showed significant correlation with MD (p=0.012), PSD (p=0.035), VFI (p=0.042) and MD (p=0.016), PSD (p=0.035), VFI (p=0.031) in the COD and COV group, respectively. No correlation was found between angle α and the presence of central scotoma in both groups. Our novel method was more convenient in a clinical setting and noninferior to the original method.

Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study

Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. ClinicalTrials.gov Identifier: NCT00212134.

Temporal Raphe Sign in Elderly Patients With Large Optic Disc Cupping: Its Evaluation as a Predictive Factor for Glaucoma Conversion

To determine baseline clinical features associated with conversion to glaucoma in elderly patients with large optic-disc cupping. Retrospective cohort study. Seventy-two eyes of 72 untreated elderly (≥65-year-old) patients with large vertical cup-to-disc ratio (CDR ≥0.7) and without any other glaucomatous findings were included. They had undergone a full ophthalmologic examination twice per year for at least 5 years. The optic nerve head (ONH), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell-inner plexiform layer (GCIPL) were imaged with Cirrus high-definition optical coherence tomography (OCT). Presence of temporal raphe sign on the OCT's GCIPL thickness map was assessed as one of the morphologic factors. Conversion to normal-tension glaucoma (NTG) was defined as structural or functional deterioration on either red-free RNFL photography or standard automated perimetry, respectively. The utility of the baseline factors associated with conversion to NTG were identified. During the 5.5-year follow-up, 19 eyes (26.4%) converted to NTG. There were no significant differences in demographics, systemic factors, intraocular pressure factors, or OCT parameters between the nonconverters and converters. Interestingly, the temporal raphe sign was observed in the converters (18/19, 94.7%) much more frequently than in the nonconverters (3/53, 5.7%, P < .001) at baseline. A Cox proportional hazards model indicated the significant influences of temporal raphe sign positivity (hazard ratio 6.823, 95% confidence interval 2.574, 18.088, P < .001) on conversion to NTG. In elderly subjects with large CDR, temporal raphe sign positivity on the baseline macular GCIPL thickness map was associated with faster conversion to NTG.

Deep optic nerve head morphology and glaucoma progression in eyes with and without laminar dot sign: a longitudinal comparative study.

To investigate the association between the laminar dot sign (LDS) and the deep optic nerve head (ONH) structure in eyes with primary-open-angle glaucoma (POAG). Eighty-four eyes of 84 patients with POAG were prospectively included. All of the patients underwent stereo optic disc photography (SDP), red-free retinal nerve fibre layer (RNFL) photography, SS-OCT, and standard automated perimetry. By evaluating the SDP, patients were classified into laminar dot sign (LDS) and non-LDS groups. The deep structure of the ONH including the anterior prelaminar depth (APLD) and prelaminar tissue thickness (PTT) were quantitated using SS-OCT. Progression was assessed by structural or functional deterioration during the average 4.3 ± 1.2 years of follow-up. The LDS group had deeper APLD (405.47 ± 107.55 vs. 302.45 ± 149.51, P < 0.001) and thinner PTT (74.34 ± 24.46 vs. 137.29 ± 40.07, P = 0.001) relative to the non-LDS group. By multivariate analysis, thin PTT was significantly associated with the presence of LDS (odds ratio = 0.939, P < 0.001). Structural progression was detected in 45 eyes (84.9%) in the LDS group and 8 eyes (25.8%) in the non-LDS group. Functional progression was demonstrated in 29 eyes (34.5%) in the LDS group and 6 eyes (19.4%) in the non-LDS group. The eyes with LDS had a significantly higher risk of glaucoma progression (χ2 = 5.00, degree of freedom = 1, P = 0.033). In eyes with POAG, the presence of LDS was associated with thinner prelaminar tissue and faster disease progression.

Defective angles of localized retinal nerve fiber layer reflect the severity of visual field defect- a cross-sectional analysis

BackgroundIn order to detect glaucomatous optic nerve damages early on and evaluate the severity of glaucoma, a previously developed analytic method based on photographic retinal nerve fiber layer (RNFL) angle defect was proposed. However, the correlation between these defective angles and the severity of visual field defect has not been verified. This study aimed to confirm the correlation described above.MethodsWe reviewed a total of 227 glaucomatous eyes (38 enrolled, 189 excluded) during an interval of 5 years. The angles of all eyes were measured on RNFL photograph, of which angle α is the angular width between the macula center and the proximity of RNFL defect, and angle β (+c) is the sum of angular width(s) of localized RNFL defect. The severity of visual field defect was determined by mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Correlation analysis was performed on angle α and angle β (+c) with the presence of central scotoma and visual field defect parameters, respectively.ResultsAngle β (+c) showed significant correlation with MD (P = 0.007), PSD (P = 0.02), VFI (P = 0.03), and average RNFL thickness (P = 0.03). No correlation was found between angle α and the presence of central scotoma.ConclusionsIn conclusion, measuring the angular width of localized RNFL defect is a viable method for determining the severity of visual field defect.

Pre-perimetric Open Angle Glaucoma with Young Age of Onset: Natural Clinical Course and Risk Factors for Progression

To investigate the natural clinical course of more than 5 years and the risk factors of progression in patients with pre-perimetric open angle glaucoma (OAG) of "young age of onset (under age 40)" without treatment. Retrospective observational case series. Optic disc photography, red-free retinal nerve fiber layer (RNFL) photography, optical coherence tomography, and visual field (VF) examinations were performed every 6months. Glaucoma progression was defined as structural or functional deterioration. A linear mixed-effects model was used to estimate the rate of structural and functional changes. Kaplan-Meier survival analysis and log-rank testing were used to compare survival experiences, and Cox proportional hazards modeling was performed to identify risk factors for glaucoma progression. Of the 98 eyes of 98 patients (mean age, 30.6 years old), glaucoma progression was detected in 42 eyes (42.9%). The rate of average RNFL thickness thinning was-0.46 ± 0.50μm/y, and the mean deviation (MD) change was-0.03 ± 0.13 dB/y. The glaucoma progression probability at 5 years was 39% by structural criteria and 5% by functional criteria. Older age at diagnosis (P= .004), presence of temporal raphe sign (horizontal straight line on macular ganglion cell-inner plexiform layer thickness map) (P= .011), lamina pore visibility (P= .034), and greater pattern standard deviation (P= .005) were significant factors for glaucoma progression. In untreated pre-perimetric OAG patients with a "young age of onset" condition, the estimated MD slope for the disease course of more than 5 years was-0.03 dB/y, and the average RNFL thinning rate was-0.46μm/y. The predictors for progression were structural parameters of temporal raphe sign, lamina pore visibility, and functional parameter of pattern standard deviation.

Macular Ganglion Cell-Inner Plexiform Layer Thickness Prediction from Red-free Fundus Photography using Hybrid Deep Learning Model

We developed a hybrid deep learning model (HDLM) algorithm that quantitatively predicts macular ganglion cell-inner plexiform layer (mGCIPL) thickness from red-free retinal nerve fiber layer photographs (RNFLPs). A total of 789 pairs of RNFLPs and spectral domain-optical coherence tomography (SD-OCT) scans for 431 eyes of 259 participants (183 eyes of 114 healthy controls, 68 eyes of 46 glaucoma suspects, and 180 eyes of 99 glaucoma patients) were enrolled. An HDLM was built by combining a pre-trained deep learning network and support vector machine. The correlation coefficient and mean absolute error (MAE) between the predicted and measured mGCIPL thicknesses were calculated. The measured (OCT-based) and predicted (HDLM-based) average mGCIPL thicknesses were 73.96 ± 8.81 µm and 73.92 ± 7.36 µm, respectively (P = 0.844). The predicted mGCIPL thickness showed a strong correlation and good agreement with the measured mGCIPL thickness (Correlation coefficient r = 0.739; P < 0.001; MAE = 4.76 µm). Even when the peripapillary area (diameter: 1.5 disc diameters) was masked, the correlation (r = 0.713; P < 0.001) and agreement (MAE = 4.87 µm) were not changed significantly (P = 0.378 and 0.724, respectively). The trained HDLM algorithm showed a great capability for mGCIPL thickness prediction from RNFLPs.

Diagnostic performance of modern imaging instruments in glaucoma screening

AimTo evaluate the applicability of imaging devices (spectral-domain optical coherence tomography (Cirrus SD-OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph, HRT3)) for glaucoma screening in a...

Progressive Optic Disc Tilt in Young Myopic Glaucomatous Eyes.

PurposeTo explore the progressive change and associated factors of optic disc tilt in young myopic glaucomatous eyes by analyzing long-term follow-up data.MethodsOptic disc images were obtained from spectral-domain optical coherence tomography enhanced depth imaging from at least five different visits. At each visit, the disc tilt angle (DTA), defined as the angle between the Bruch's membrane opening plane and the optic canal plane, was estimated at the central frame that passes through the optic disc. Glaucoma progression was assessed on the basis of changes noted on serial optic disc and retinal nerve fiber layer photographs or changes in the visual field (VF). A linear mixed effect model was used to assess the influence of parameters (age, sex, baseline and follow-up intraocular pressure, retinal nerve fiber layer thickness, VF mean deviation, axial length, central corneal thickness), and presence of glaucomatous progression upon DTA change.ResultsA total of 26 eyes of 26 young myopic primary open-angle glaucoma patients (axial length >24.0 mm; mean age, 25.1 ± 4.0 years; mean follow-up, 3.3 ± 0.9 years) were included. DTA was 7.0 ± 3.4 degrees at baseline and 8.3 ± 3.8 degrees at last visit, which represents a significant difference (p < 0.001). Worse VF mean deviation (p < 0.001) and longer axial length (p = 0.006) were significantly associated with DTA increase.ConclusionsYoung myopic glaucomatous eyes showed progressive optic disc tilting. Progressive optic disc tilting in young myopic glaucomatous eyes may be related to either continuous axial myopic shift or glaucomatous structural change.

A study for the assessment of central corneal thickness and visual field defects in patients of primary open-angle glaucoma

Purpose: The aim of this study is to assess the central corneal thickness (CCT) and visual field (VF) changes in patients of primary open-angle glaucoma (POAG) and the influence of CCT on glaucomatous damage in glaucoma clinic of Dr. R. P. G. M. C Kangra at Tanda. Materials and Methods: This cross-sectional study conducted on 103 eyes of 58 patients of POAG- >40 years. All patients underwent a complete eye examination including Goldmann applanation tonometry, CCT measurement through ultrasonic pachymeter, stereoscopic disc photography, retinal nerve fiber layer (RNFL) photography, and automated perimetry. Correlation of CCT with age, gender, intraocular pressure (IOP), advanced glaucoma intervention study (AGIS) score, VF parameters (mean deviation, pattern standard deviation [PSD]), vertical cup-disc ratio, average RNFL, and number of antiglaucoma medications was analyzed. The patients were divided into two groups – thin and thick CCT taking a reference range of 529 μm derived from a previous study done in same area with larger sample size. Pearson correlation was used for correlation coefficient and a value of P < 0.05 was considered statistically significant. Results: Thin CCT was significantly correlated with IOP (r = 0.28, P = 0.004). Thin CCT was also significantly associated with worsened PSD of VF (r = 0.25, P = 0.02). The mean AGIS score was more (8.07 ± 5.52) in patients with thin CCT (<529 μm) in comparison (5.96 ± 6.10) to patients with thick CCT (>529 μm) which was statistically significant (P < 0.05). Conclusion: CCT is a significant risk factor for glaucomatous VF loss. Patients with thinner CCT are more likely to have advanced VF defects in comparison to patients with thick CCT.

Effect of Antiplatelet/Anticoagulant Use on Glaucoma Progression in Eyes With Optic Disc Hemorrhage.

To assess whether the use of antiplatelets (APs)/anticoagulants (ACs) affects glaucoma progression in eyes with optic disc hemorrhage (DH). One hundred and nineteen eyes from 119 patients with primary open-angle glaucoma in whom a DH was observed at least once during the follow-up period (mean follow-up duration: 6.2 y) were included in this retrospective observational study. Cox proportional hazard models were used to identify the association between putative factors, including AP/AC use, and glaucoma progression. Glaucoma progression was assessed on the basis of changes noted on serial optic disc and retinal nerve fiber layer photographs or changes in the visual field. Nineteen of the 119 patients took AP/AC drugs daily [AP/AC use group (AG)], while the others did not [no use group (NG)]. The follow-up period to progression was significantly different between the 2 groups (61.2±23.5 mo for the AG and 47.6±22.0 mo for the NG; P=0.016). Kaplan-Meier analysis revealed a greater cumulative probability of glaucoma progression in the NG than in the AG, with borderline statistical significance (P=0.081). Higher mean intraocular pressure during the follow-up period was a risk factor for glaucoma progression (hazard ratio, 1.107; P=0.014), while AP/AC drug use protected against glaucoma progression (hazard ratio, 0.576; P=0.046). According to our result, use of AP/AC drugs was associated with lower risk of glaucoma progression in eyes with DH.

Prevalence of glaucoma in the Northern Finland Birth Cohort Eye Study

To report the prevalence of glaucoma in the Northern Finland Birth Cohort (NFBC) Eye Study. Subjects of the population-based Northern Finland 1966 Birth Cohort (NFBC), aged 45-49years at the time of the field examination, were randomized to eye screening (50%) and control (50%) groups. The eye examination protocol included best corrected visual acuity (BCVA), measurements of intraocular pressure and central corneal thickness, Humphrey 24-2 perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with optical coherence tomography (OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (HRT). The diagnosis of glaucoma was made by two independent general ophthalmologists and three independent glaucoma experts based on the evaluation of the ONH and RNFL photographs and the visual fields. Totally, 10321 subjects of the NFBC main study were alive in Finland in 2011, and they were randomized to the NFBC Eye Study group (n=5155) and the control group (n=5166). Of the randomized subjects, 3039 of 5155 (59%) responded and had sufficient data for the study. Glaucoma was suspected in 172 subjects (5.7%) at the first phase of the evaluation protocol. The interobserver agreement between two screening ophthalmologists was moderately good (kappa value 0.54 [95% confidence intervals (CI) 0.46-0.61]). Finally, definite glaucoma was found in 33 subjects (1.1% [95% CI 0.8-1.5]). The study provides up-to-date information on the prevalence of glaucoma in a middle-aged Caucasian population in Finland. The baseline data reported here allows the evaluation of the cost-effectiveness of screening later on.