Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. DESIGN: Cross-sectional study. PARTICIPANTS: Six hundred eyes of 306 patients with OHT. METHODS: All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. MAIN OUTCOME MEASURES: Prevalence of RNFL defects. RESULTS: The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 µm and 568.8 ± 31.2 µm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. CONCLUSIONS: A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessment of Iris Trabecular Contact in Eyes with Gonioscopic Angle-Closure.

PURPOSE: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. DESIGN: Multicenter, prospective study. PARTICIPANTS: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. METHODS: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. MAIN OUTCOME MEASURES: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. RESULTS: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm2), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). CONCLUSIONS: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.

Retinal Nerve Fiber Layer Optical Texture Analysis: Involvement of the Papillomacular Bundle and Papillofoveal Bundle in Early Glaucoma.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) in eyes with early glaucoma to investigate (1) the pattern of RNFL defects, (2) how often the papillomacular bundle and papillofoveal bundles are involved, and (3) the association between papillomacular and papillofoveal bundle defects and visual field (VF) sensitivity abnormalities. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred four eyes with early glaucoma (VF mean deviation, ≥ -6 dB) with RNFL defects from 171 consecutively enrolled patients with glaucoma. METHODS: All eyes underwent 24-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate bundle, papillomacular bundle (i.e., bundles from the macula, excluding the fovea), and papillofoveal bundle (i.e., bundles from the fovea) was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association. MAIN OUTCOME MEASURES: Proportions of eyes with papillomacular or papillofoveal bundle defects. RESULTS: Of the 204 eyes, 71.6% and 17.2% demonstrated RNFL defects involving the papillomacular and papillofoveal bundles, respectively; 25.0% showed arcuate bundle defects without involvement of papillomacular or papillofoveal bundles. The pattern of RNFL defects was diverse; the most common was concomitant involvement of the inferior arcuate bundle and the inferior papillomacular bundle (20.6%). Papillomacular or papillofoveal bundle defects were not associated with VF defects (i.e., with ≥ 3 contiguous locations with abnormal VF sensitivity in the pattern deviation probability plot) in the corresponding hemifield, although VF sensitivity of any 1 of the central 4 VF locations of the 24-2 test, which were within the macula, was more likely to be abnormal (P < 0.05 in the pattern deviation probability plot; odds ratio, 12.5; 95% confidence interval, 7.0-22.5) when the VF stimulus was projected onto a papillomacular or papillofoveal bundle defect than that projected onto an intact papillomacular or papillofoveal bundle. CONCLUSIONS: Contrary to the conventional notion that the fovea and macula are not affected until the late stages of glaucoma, papillofoveal and papillomacular bundle defects were common in early glaucoma, and they were associated with central VF sensitivity loss at the corresponding VF test locations.

Diagnostic criteria of anterior segment swept-source optical coherence tomography to detect gonioscopic angle closure.

AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.

Reproducibility of deep learning based scleral spur localisation and anterior chamber angle measurements from anterior segment optical coherence tomography images.

AIMS: To apply a deep learning model for automatic localisation of the scleral spur (SS) in anterior segment optical coherence tomography (AS-OCT) images and compare the reproducibility of anterior chamber angle (ACA) width between deep learning located SS (DLLSS) and manually plotted SS (MPSS). METHODS: In this multicentre, cross-sectional study, a test dataset comprising 5166 AS-OCT images from 287 eyes (116 healthy eyes with open angles and 171 eyes with primary angle-closure disease (PACD)) of 287 subjects were recruited from four ophthalmology clinics. Each eye was imaged twice by a swept-source AS-OCT (CASIA2, Tomey, Nagoya, Japan) in the same visit and one eye of each patient was randomly selected for measurements of ACA. The agreement between DLLSS and MPSS was assessed using the Euclidean distance (ED). The angle opening distance (AOD) of 750 µm (AOD750) and trabecular-iris space area (TISA) of 750 µm (TISA750) were calculated using the CASIA2 embedded software. The repeatability of ACA width was measured. RESULTS: The mean age was 60.8±12.3 years (range: 30-85 years) for the normal group and 63.4±10.6 years (range: 40-91 years) for the PACD group. The mean difference in ED for SS localisation between DLLSS and MPSS was 66.50±20.54 µm and 84.78±28.33 µm for the normal group and the PACD group, respectively. The span of 95% limits of agreement between DLLSS and MPSS was 0.064 mm for AOD750 and 0.034 mm2 for TISA750. The respective repeatability coefficients of AOD750 and TISA750 were 0.049 mm and 0.026 mm2 for DLLSS, and 0.058 mm and 0.030 mm2 for MPSS. CONCLUSION: DLLSS achieved comparable repeatability compared with MPSS for measurement of ACA.

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.

Use of Virtual Reality Simulation to Identify Vision-Related Disability in Patients With Glaucoma.

Importance: Clinical assessment of vision-related disability is hampered by the lack of instruments to assess visual performance in real-world situations. Interactive virtual reality (VR) environments displayed in a binocular stereoscopic VR headset have been designed, presumably simulating day-to-day activities to evaluate vision-related disability. Objective: To investigate the application of VR to identify vision-related disability in patients with glaucoma. Design, Setting, and Participants: In a cross-sectional study, 98 patients with glaucoma and 50 healthy individuals were consecutively recruited from a university eye clinic; all participants were Chinese. The study was conducted between August 30, 2016, and July 31, 2017; data analysis was performed from December 1, 2017, to October 30, 2018. Exposures: Measurements of visual acuity, contrast sensitivity, visual field (VF), National Eye Institute 25-item Visual Function Questionnaire Rasch score, and VR disability scores determined from 5 VR simulations: supermarket shopping, stair and city navigations in daytime, and stair and city navigations in nighttime. Duration required to complete the simulation, number of items incorrectly identified, and number of collisions were measured to compute task-specific and overall VR disability scores. Vision-related disability was identified when the VR disability score was outside the normal age-adjusted 95% confidence region. Main Outcomes and Measures: Virtual reality disability score. Results: In the 98 patients with glaucoma, mean (SD) age was 49.8 (11.6) years and 60 were men (61.2%); in the 50 healthy individuals, mean (SD) age was 48.3 (14.8) years and 16 were men (32.0%). The patients with glaucoma had different degrees of VF loss (122 eyes [62.2%] had moderate or advanced VF defects). The time required to complete the activities by patients with glaucoma vs healthy individuals was longer by 15.2 seconds (95% CI, 5.5-24.9 seconds) or 34.1% (95% CI, 12.4%-55.7%) for the shopping simulation, 72.8 seconds (95% CI, 23.0-122.6 seconds) or 33.8% (95% CI, 10.7%-56.9%) for the nighttime stair navigation, and 38.1 seconds (95% CI, 10.9-65.2 seconds) or 30.8% (95% CI, 8.8%-52.8%) for the nighttime city navigation. The mean (SD) duration was not significantly different between the glaucoma and healthy groups in daytime stair (203.7 [93.7] vs 192.9 [89.1] seconds, P = .52) and city (118.7 [41.5] vs 117.0 [52.3] seconds, P = .85) navigation. For each decibel decrease in binocular VF sensitivity, the risk of collision increased by 15% in nighttime stair (hazard ratio [HR], 1.15; 95% CI, 1.08-1.22) and city (HR, 1.15; 95% CI, 1.08-1.23) navigations. Fifty-eight patients (59.1%) with glaucoma had vision-related disability in at least 1 simulated daily task; a higher proportion of patients had vision-related disability in nighttime city (27 of 88 [30.7%]) and stair (27 of 90 [30.0%]) navigation than in daytime city (7 of 88 [8.0%]) and stair (19 of 96 [19.8%]) navigation. The overall VR disability score was associated with the National Eye Institute 25-item Visual Function Questionnaire Rasch score (R2 = 0.207). Conclusions and Relevance: These findings suggest that vision-related disability is associated with lighting condition and task in patients with glaucoma. Virtual reality may allow eye care professionals to understand the patients' perspectives on how visual impairment imparts disability in daily living and provide a new paradigm to augment the assessment of vision-related disability.