Retinal Nerve Fiber Layer Imaging Research Articles

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell Complex Rates of Change in Patients With Moderate to Advanced Glaucoma

PurposeTo compare ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) rates of change (RoC) in eyes with central or moderate to advanced glaucoma. DesignProspective cohort study. Participants918 matched macular and RNFL OCT scan pairs from 109 eyes (109 patients) enrolled in the Advanced Glaucoma Progression Study with ≥2 years of follow-up and ≥4 OCT scans. MethodsWe exported GCC and RNFL thickness measurements in 49 central macular superpixels and 12 RNFL clock-hour sectors, respectively. We applied our latest Bayesian hierarchical longitudinal model to estimate population and subject-specific baseline thickness (intercepts) and rates of change (RoC) in macular superpixels and RNFL sectors. Global RNFL and GCC RoC were analyzed in a single bivariate longitudinal model to properly compare them accounting for the correlation between their RoC. Main Outcome MeasuresProportion of significant negative (deteriorating) and positive (improving) RoC expressed in μm/year. Standardized RoC were calculated by dividing RoC by the corresponding population SD. Analyses were repeated in eyes with visual field mean deviation (MD) ≤–6 and >–6 dB. ResultsAverage (SD) 24-2 visual field MD and follow-up length were –8.6 (6.3) dB and 4.2 (0.5) years, respectively. Global RNFL RoC (–0.70 µm/year) were faster than GCC (–0.44 µm/year) (p<.001); corresponding normalized RoC were not significantly different (p=0.052). In bivariate analysis, patients with a significant negative global RNFL RoC (n=63, 57%) or GCC (n=56, 51%) frequently did so for both outcomes (n=49, 45%). The average proportion of significantly decreasing RNFL sectors within an eye was 30.7% in eyes with MD >–6 dB compared to 20.5% in those with MD ≤–6 dB (p=0.014); the proportions for GCC superpixels were 21.1% vs. 18.7%, respectively (p=0.63). ConclusionsBoth GCC and RNFL measures can detect structural progression in glaucoma patients with central damage or moderate to advanced glaucoma. The clinical utility of RNFL imaging decreases with worsening severity of glaucoma.

THE EFFECT OF INTERNAL LIMITING MEMBRANE PEELING ON THE INNER RETINAL LAYERS IN PATIENTS WITHOUT MACULAR PATHOLOGIC CONDITION.

To examine the effect of internal limiting membrane peeling on the inner retinal layers in patients without macular pathological condition. A prospective nonrandomized trial of patients undergoing pars plana vitrectomy with internal limiting membrane peeling for pathologic condition outside the macula was performed. Optical coherence tomography including macular ganglion cell layer, inner plexiform layer, and peripapillary retinal nerve fiber layer imaging was performed before surgery, 1, 3, and 6 months postoperatively, and at the end of follow-up (ranges between 4 and 17 months). Patients with any macular pathological condition on optical coherence tomography before surgery were excluded. The main outcome measure was change in thickness of the ganglion cell layer and inner plexiform layer. Ten patients who underwent pars plana vitrectomy with internal limiting membrane peeling for macula-on retinal detachment were included in the analysis. The mean age was 55 years, and the mean follow up was 10.8 months. All patients completed at least two postoperative follow-up visits that included an optical coherence tomography as per the protocol (range 2-6 months). There was an immediate reduction in the global (G), inferotemporal, superotemporal, and superior (S) ganglion cell layer thickness at the first follow up as compared with the preoperative state ( P = 0.028, P = 0.027, P = 0.026, and P = 0.027 respectively). From the first follow-up visit onward until the final follow-up, the thinning persisted, although there was no further statistically significant thinning. Peeling of the internal limiting membrane causes significant ganglion cell layer thinning in maculae without pathologic condition before surgery. At up to 17 months of follow-up, this effect seems to be immediate and nonprogressive.

Retinal Nerve Fiber Layer Thickness in Patients with Schizophrenia and Its Relation with Cognitive Impairment.

Schizophrenia is a chronic severe mental illness with heterogeneous clinical presentation, course, and outcome. Cognitive impairment is one of its core features. Retinal nerve fiber layer (RNFL) imaging using OCT (optical coherence tomography) could provide easy access for in vivo imaging of the retina, rendering it as a "window to the brain." Studies done on schizophrenia have shown RNFL thinning. This study attempts to look into the association between cognitive impairment, disease duration, and RNFL abnormality in patients with schizophrenia using OCT. Patients diagnosed with schizophrenia meeting DSM 5 (Diagnostic and Statistical Manual of Mental Disorders) criteria and who were confirmed to be in remission for at least six months clinically and scoring less than three on PANSS-8 (positive and negative symptom scale-8) remission scale were included. They were administered the Montreal Cognitive Assessment Scale (MoCA) for cognitive assessment. RNFL measures were taken using spectral domain-OCT. Variables were compared using Pearson's correlation test, one-way ANOVA test, and independent t-test as appropriate. A total of 36 patients were studied. MoCA scores and RNFL thickness showed a positive correlation. Patients with schizophrenia had reduced average RNFL thickness and reduced RNFL thickness in superior, inferior, and temporal quadrants. Average RNFL thickness, Superior and inferior quadrant RNFL thickness showed a positive correlation with MoCA scores. No correlation was obtained between macular volume, macular thickness, duration of illness, and MoCA scores. Patients with schizophrenia have reduced average RNFL thickness. Patients with low MoCA scores have RNFL thinning.

Assessment of linear regression of peripapillary optical coherence tomography retinal nerve fiber layer measurements to forecast glacuoma trajectory.

Linear regression of optical coherence tomography measurements of peripapillary retinal nerve fiber layer thickness is often used to detect glaucoma progression and forecast future disease course. However, current measurement frequencies suggest that clinicians often apply linear regression to a relatively small number of measurements (e.g., less than a handful). In this study, we estimate the accuracy of linear regression in predicting the next reliable measurement of average retinal nerve fiber layer thickness using Zeiss Cirrus optical coherence tomography measurements of average retinal nerve fiber layer thickness from a sample of 6,471 eyes with glaucoma or glaucoma-suspect status. Linear regression is compared to two null models: no glaucoma worsening, and worsening due to aging. Linear regression on the first M ≥ 2 measurements was significantly worse at predicting a reliable M+1st measurement for 2 ≤ M ≤ 6. This range was reduced to 2 ≤ M ≤ 5 when retinal nerve fiber layer thickness measurements were first "corrected" for scan quality. Simulations based on measurement frequencies in our sample-on average 393 ± 190 days between consecutive measurements-show that linear regression outperforms both null models when M ≥ 5 and the goal is to forecast moderate (75th percentile) worsening, and when M ≥ 3 for rapid (90th percentile) worsening. If linear regression is used to assess disease trajectory with a small number of measurements over short time periods (e.g., 1-2 years), as is often the case in clinical practice, the number of optical coherence tomography examinations needs to be increased.

Artifacts in OCT Retinal Nerve Fiber Layer Imaging in Patients with Boston Keratoprosthesis Type 1

To determine the clinical utility of optical coherence tomography retinal nerve fiber layer (OCT RNFL) imaging for glaucoma evaluation in patients with Boston keratoprosthesis type 1 (KPro) by investigating imaging artifacts. Case-control study. Patients with KPro and without KPro (controls) matched for age, gender, and glaucoma diagnosis. The most recent Cirrus OCT RNFL scan from one eye was categorized as with good signal strength (SS; ≥6 out of 10) or poor SS (<6). Those with good SS were analyzed by two independent reviewers for artifacts. Images with good SS and no artifacts affecting the scanning circle were considered useful for glaucoma evaluation. The incidence of poor SS and artifacts in OCT RNFL images; patient characteristics associated with useful scans. Sixty-five patients with KPro and 75 controls were included; 89.2% of KPro patients and 89.3% of control subjects had glaucoma (p=0.98). 40.0% of KPro patients and 5.3% of controls had poor SS (p<0.001). The proportion of images with either poor SS or artifacts was similar in KPro (76.9%) versus controls (72.0%, p=0.51). The most common artifacts in both groups were missing data (43.6%, 53.2%, respectively, p=0.32) and motion artifact (25.6%, 19.7%, respectively, p=0.47). 43.1% of images in KPro patients and 69.3% in controls were useful for glaucoma evaluation (p=0.002). In the KPro group, patients with useful OCT scans, compared to those without, had better visual acuity (0.4±0.3 vs. 0.9±0.7 LogMAR, p=0.004), and did not have congenital corneal pathologies (0.0% vs. 24.3%, p=0.008). A multivariable analysis showed KPro patients with older age had higher odds of useful OCT images (odds ratio 1.05, p=0.03). Among KPro patients with useful OCT scans, RNFL thickness correlated with observed cup to disc ratio (Pearson correlation r=-0.42, p=0.03). The rate of OCT RNFL images with either poor signal strength or artifacts in the KPro and control population was comparable. In patients with KPro, where intraocular pressure measurements are difficult and glaucoma is highly prevalent and often severe, OCT RNFL imaging can be useful for glaucoma evaluation.

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

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. Cross-sectional study. Six hundred eyes of 306 patients with OHT. 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. Prevalence of RNFL defects. 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. 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal Nerve Fiber Layer Imaging with Two Different Spectral Domain Optical Coherence Tomographs: Normative Data for Romanian Children.

The purpose of this study is to analyze and compare pediatric normative data for the retinal nerve fiber layer of Romanian children using two different spectral domain optical coherence tomographs. Due to different scanning speeds and axial and transverse resolution, the results of the measurements of scans cannot be transposed. A total of 140 healthy children aged 4 to 18 were enrolled in the study. Overall, 140 eyes were scanned with a Spectralis SD-OCT (Heidelberg Technology), and the other 140 eyes were imaged with a Copernicus REVO SOCT (Optopol Technology (Zawiercie, Poland)). The mean global RNFL thickness and average RNFL thickness for the four quadrants were measured and compared. The average peripapillary RNFL thickness measured with the Spectralis was 104.03 ± 11.42 (range 81 to 126 µm), while the one measured with the Revo 80 was 127.05 ± 15.6 (range 111.43-158.28). The RNFL thickness measurements taken with the Spectralis in the superior, inferior, nasal, and temporal quadrants were 132 ±19.1, 133.5 ± 21.77, 74 ± 16.48, and 73 ± 11.95 µm, respectively, while those taken with the Revo 80 were 144.44 ± 9.25, 144.86 ±23.12, 96.49 ± 19.41, and 77 ± 11.4 µm, respectively. Multivariate analysis showed that the average RNFL thickness was not influenced by gender or eye laterality and was negatively correlated with age when we used the Spectralis device. This study provides normative data for SD-OCT peripapillary RNFL in healthy Romanian children for two different tomographs. These data help the clinician evaluate and interpret the results of optical coherence tomography for a child, taking into consideration all the technical and individual parameters.

Venous Sinus Stenting for Low Pressure Gradient Stenoses in Idiopathic Intracranial Hypertension.

Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response. To explore the possibility of benefit in low venous pressure gradient patients. Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and neuro-ophthalmological outcomes (including optical coherence tomography and Humphrey visual fields) were compared. Among 53 patients, the mean age was 32 years and 70% female with a mean body mass index was 36 kg/m 2 . Baseline characteristics were similar between groups. The mean change in lumbar puncture opening pressure at 6 months poststenting was similar between the 3 groups (≤4, 5-8, and >8 mmHg; 13.4, 12.9, and 12.4 cmH 2 O, P = .47). Papilledema improvement was observed across groups at 6 months (100, 93, and 86, P = .7) as were all clinical symptoms. The mean changes in optical coherence tomography retinal nerve fiber layer (-30, -54, and -104, P = .5) and mean deviation in Humphrey visual fields (60, 64, and 67, P = .5) at 6 weeks were not significantly different. Patients with IH with low venous pressure gradient venous sinus stenosis seem to benefit equally from venous stenting compared with their higher gradient counterparts. Re-evaluation of our restrictive criteria for this potentially vision sparing intervention is warranted. Future prospective confirmatory studies are needed.

Patterns of Optical Coherence Tomography Imaging in Preperimetric Open Angle Glaucoma: A Comparative Study With Young-Age-Onset and Old-Age-Onset Eyes.

Optic coherence tomography imaging in preperimetric open angle glaucoma (OAG) differed between young-age-onset and old-age-onset eyes. Inferior and superior quadrants were thinner in young and old-age-onset eyes, respectively. Understanding the specific patterns of early glaucomatous damage based on age-at-onset may improve glaucoma diagnosis and monitoring. To investigate the patterns of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning in preperimetric OAG by optical coherence tomography based on age at onset ("young-age onset (<40y)" vs. "old-age onset (≥40y)". The RNFL and GCIPL deviation images were acquired by Cirrus HD-optical coherence tomography, and overlaid, thus converted to a "deviation frequency map", respectively. The topographic thinning patterns and parameters of RNFL and GCIPL thickness measurements were compared. A total of 194 eyes of 194 patients with preperimetric OAG and 97 eyes of 97 age-matched normal subjects were analyzed. Young-age-onset eyes of preperimetric OAG mainly had RNFL defects inferotemporally (264-296 degrees) with GCIPL defects in the inferior region (213-357 degrees). Old-age-onset preperimetric OAG eyes had RNFL defects inferotemporally (266-294°) and superotemporally (33-67 degrees), with GCIPL defects in the inferior and superior regions (206-360 degrees, 0-22 degrees). The inferior quadrant of RNFL and GCIPL thicknesses were significantly thinner in young-age-onset eyes compared with old-age-onset eyes ( P =0.012, 0.016), while the superior quadrant of those were significantly thinner in the old-age-onset eyes ( P =0.003, 0.005). Young-age-onset and old-age-onset eyes of preperimetric OAG present different specific patterns of RNFL and GCIPL thinning.

Adaptive optics scanning laser ophthalmoscopy may support early diagnosis of glaucoma.

To compare image characteristics of retinal nerve fiber layer (RNFL) between glaucoma patients and healthy controls using adaptive optics scanning laser ophthalmoscopy (AOSLO). This was a cross-sectional pilot study with two groups: a glaucoma group with patients with moderate or severe glaucoma as per the Hodapp-Parrish-Anderson classification system and a control group with healthy individuals. The optic nerve damage in moderate glaucoma was predominantly located in only one hemisphere; the other hemisphere was un- or minimally affected on optical coherence tomography and automated perimetry and is referred to as early glaucoma. The structure of RNFL bundles and gain (%) in RNFL images with mean pixel values between 15 and 35 were analyzed. Imaging was performed one degree away from the optic disc margin at two and four cardinal clock positions in the glaucoma and control groups, respectively. The field of view was 1.3° at 2.3 μ resolution. We studied one eye per participant. There were 11 glaucoma patients and 7 healthy controls. Imaging was successful at 88% of the locations in controls and early glaucoma; the reflectivity differed significantly (0.51 and 0.56, respectively, P < 0.001) but not the structure of RNFL bundles (Cohen's Kappa 0.11) between them. In patients with moderate and severe glaucoma, imaging was successful only at 46% of the locations; RNFL bundles were not discernible, and RNFL reflectivity did not differ from those with early glaucoma (P < 0.11). The recorded gain (%) of RNFL images obtained using AOSLO could be an objective indicator of early glaucoma.

Optical coherence tomography angiography and Humphrey visual field in patients with obstructive sleep apnea.

To determine if obstructive sleep apnea syndrome (OSAS) predisposes patients to glaucoma and macular disease due to vascular compromise by evaluating retinal and optic nerve vasculature and function using optical coherence tomography angiography and Humphrey visual field testing, respectively. In this prospective, observational, cross-sectional study 45 patients undergoing polysomnography ordered per standard of care were selected and stratified based on apnea-hypopnea index (AHI). Medical history, visual acuity testing, 24-2 Humphrey visual field, intraocular pressure measurement, and optical coherence tomography angiography studies of the macular and peripapillary retina were obtained. Correlations between polysomnography parameters and imaging data were analyzed. The radial peripapillary capillary vascular density demonstrated no relationship to AHI (95% confidence interval [CI] [-0.026,0.038]) or severity of OSAS (95% CI: [-0.772, 3.648]) for moderate OSAS compared to mild/normal and (-1.295, 3.1421) for severe compared to mild/normal. Optical coherence tomography angiography superficial parafoveal vascular density (95% CI: [-0.068,0.011], deep parafoveal vascular density (95% CI: [-0.080,0.009]), and foveal avascular zone (95% CI: [-0.001, 0.001]) showed no statistically significant relationship to AHI or OSAS severity after controlling for confounders. Optical coherence tomography retinal nerve fiber layer thickness increased with AHI (P = .014), but there was no statistically significant correlation with OSAS severity with retinal nerve fiber layer thickness (95% CI: [-12.543, 6.792] for moderate comparing to normal and [-2.883, 16.551] for severe comparing to normal). Visual field parameters were unaffected by OSAS (95% CI: mean deviation [-0.21,0.29], pattern standard deviation: [-0.351, 0.121], visual field index: [-0.166, 0.329]). Optical coherence tomography choroidal thickness showed a statistically significant decrease when OSAS was grouped by severity (P = .0092) but did not correlate with AHI (P = .129, 95% CI: [-1.210, 0.095]). The severity of OSAS did not show a statistically significant effect on parameters associated with glaucoma or macular vascular disease. Larger cohorts may be required to determine the physiologic consequences of OSAS on the macular and optic nerve vasculature, structure, and function. Davanian A, Williamson L, Taylor C, etal. Optical coherence tomography angiography and Humphrey visual field in patients with obstructive sleep apnea. J Clin Sleep Med 2022;18(9):2133-2142.

Peripapillary vessel density correlates with visual field mean sensitivity in highly myopic eyes

PurposeTo identify the global and regional distribution of peripapillary vessel density (pVD) and try to find out the relationships between pVD and the visual field mean sensitivity (VFMS) in healthy myopic eyes.DesignProspective cross-sectional study.MethodsTwo hundred and twenty-two participants (393 eyes) with myopia (myopic refractive error < − 0.5 diopters) from two clinical centers were recruited in this study and were divided into 4 groups according to the spherical equivalent (SE): Group1:− 0.5D ≥ SE > − 6.00D, Group2: − 6.00D ≥ SE > − 8.00D, Group3:− 8.00D ≥ SE > − 10.00D, Group4:SE ≤ -10.00D.The pVD assessed with optical coherence tomography angiography (OCTA) was quantified in 8 sectors. Peripapillary retinal nerve fibre layer (pRNFL) imaging was performed with SD-OCT. Visual field (VF) tests were performed with the 30-2 SITA standard program on the Humphrey 750i Visual Field Analyzer and were grouped into 8 regions that matched the structure.ResultsThe pRNFL had no significant difference in all groups (p = 0.422). The average pVD were significantly lower in group 4 (47.61 ± 6.58) than in group 2 and 3 (51.49 ± 3.21, 50.48 ± 3.43 respectively) (p < 0.05). While both pVD in group2 and 3 were statistically lower than group1 (52.77 ± 2.86). The average VFMS was significantly lower in group 4 (901.85 ± 386.54) than other three groups (1169.15 ± 328.94, 1081.77 ± 338.83, 1076.89 ± 358.18, for group1,2,3 respectively). The pVD and VFMS were positively correlated in group3 (r = 0.184) and group4 (r = 0.476) (p < 0.05). Linear regression analysis demonstrated that VFMS were positively associated with pVD especially in temporal and nasal quadrants in myopic eyes.ConclusionsThe pVD shows a significant positive correlation with VFMS in highly myopic eyes with SE ≤ − 8.00D. We suggest that pVD measurement by OCTA could be a sensitive and useful method for monitoring myopic functional change.

Clinical profile and retinal nerve fibre layer thickness of optic disc oedema patients at a tertiary care institute in North India.

Background:Optic disc oedema (ODE) is an important manifestation in various ocular as well as systemic disorders. Measurement of retinal nerve fibre layer (RNFL) thickness in ODE patients may help in monitoring the progress of the disease and treatment response.Objective:To assess the clinical characteristics, aetiology and retinal nerve fibre layer (RNFL) imaging features of optic disc oedema (ODE) patients.Design:A retrospective observational study.Methods:This hospital-based study included performed for patients presenting with unilateral or bilateral ODE at the ophthalmology outpatient department of a tertiary institute between January 2019 and December 2019. Clinical features of all ODE patients were noted. RNFL thickness was measured by spectral-domain optical coherence tomography (Cirrus 500, Carl Zeiss Meditec, Dublin, CA, USA).Results:Sixty-four patients with ODE were seen with female preponderance (56.2%). The mean age of presentation was 36.8 ± 13.8 years. Bilateral ODE was seen in 57.8% patients. The most common cause of bilateral ODE was idiopathic intracranial hypertension (IIH) and vascular papillopathy. Retinal vein occlusion (RVO)-associated ODE was the most common unilateral presentation. Presenting visual acuity was best with IIH and worst with anterior ischaemic optic neuropathy (AION). The mean duration of symptoms was maximum with intracranial space-occupying lesion associated papilloedema and minimum with AION. The mean RNFL thickness was highest in uveitis-associated ODE, followed by compressive ON, and IIH. A positive correlation was noted between clinical ODE severity and RNFL thickness. All aetiological categories (except uveitic and compressive) had maximum RNFL thickening in the inferior quadrant and minimum in the temporal quadrant.Conclusion:The current study provides a clinical profile and RNFL measurements of ODE patients at this locality. The clinical severity of ODE correlated positively with RNFL thickness and most of the categories of ODE followed the normative pattern of RNFL thickness (inferior > superior > nasal > temporal) despite thickening.

Quality of referrals for glaucoma assessment: a cross-sectional survey of clinical data and outcomes.

This study assessed the completeness of clinical information provided by ophthalmological and optometric referrals to glaucoma specialists consulting for open-angle glaucoma (OAG). A retrospective, cross-sectional study of 72 internal referrals for evaluation of OAG in a multispecialty group practice was performed. The quality of the referral was assessed based on: (1) the completeness of the clinical triad of intraocular pressure measurement, visual field (VF), and cup-to-disk ratio for each eye; (2) the availability of the data necessary to calculate an ocular hypertension treatment study (OHTS) score; and (3) the presence of retinal nerve fiber layer (RNFL) imaging by mean of optical coherence tomography. The clinical triad was available in 57% of referrals, whereas an OHTS score was calculable in 24% of referrals (p < 0.001); RNLF imaging was available in 51% of referrals (p = 0.859). The completeness of clinical information was similar for ophthalmological and optometric referrals. From the date of referral to the time of the consultation, there was a significant increase in the availability of the clinical triad (57-65%; p = 0.013) and the OHTS score (24-5%; p = 0.004) but not for RNFL imaging (51-56%; p = 0.618). The most common missing clinical information was VF testing, which was absent in 42% of referrals. Key clinical data necessary for effective diagnosis and staging of OAG was lacking for many patients referred to glaucoma specialists.

Visual Field Inference From Optical Coherence Tomography Using Deep Learning Algorithms: A Comparison Between Devices.

PurposeTo develop a deep learning model to estimate the visual field (VF) from spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) and to compare the performance between them.MethodsTwo deep learning models based on Inception-ResNet-v2 were trained to estimate 24-2 VF from SS-OCT and SD-OCT images. The estimation performance of the two models was evaluated by using the root mean square error between the actual and estimated VF. The performance was also compared among different glaucoma severities, Garway-Heath sectorizations, and central/peripheral regions.ResultsThe training dataset comprised images of 4391 eyes from 2350 subjects, and the test dataset was obtained from another 243 subjects (243 eyes). In all subjects, the global estimation errors were 5.29 ± 2.68 dB (SD-OCT) and 4.51 ± 2.54 dB (SS-OCT), and the estimation error of SS-OCT was significantly lower than that of SD-OCT (P < 0.001). In the analysis of sectors, SS-OCT showed better performance in all sectors except for the inferonasal sector in normal vision and early glaucoma. In advanced glaucoma, the estimation error of the central region was worsened in both OCTs, but SS-OCT was still significantly better in the peripheral region.ConclusionsOur deep learning model estimated the VF 24-2 better with a wide field image of SS-OCT than did with retinal nerve fiber layer and ganglion cell–inner plexiform layer images of SD-OCT.Translational RelevanceThis deep learning method can help clinicians to determine the VF from OCT images. OCT manufacturers can equip this system to provide additional VF data.

Tutorial on Biostatistics: Receiver-Operating Characteristic (ROC) Analysis for Correlated Eye Data

ABSTRACT Purpose To demonstrate methods for receiver-operating characteristic (ROC) analysis of correlated eye data. Methods We applied the Obuchowski’s nonparametric approach and cluster bootstrap for estimating and comparing the area under ROC curve (AUC) between different sets of predictors to three datasets with varying inter-eye correlation. Results In an optic neuritis (ON) study of 152 eyes (80 patients), the AUC of optical coherence tomography retinal nerve fiber layer thickness for diagnosing ON (inter-eye kappa = 0.13) was 0.71 [95% confidence interval (95% CI): 0.622, 0.792] from the naïve approach without accounting for inter-eye correlation was narrower than from nonparametric (95% CI: 0.613, 0.801) or cluster bootstrap (95% CI: 0.614, 0.797) approaches. In an analysis of 198 eyes (135 patients), the baseline Age-related Eye disease Study scale predicted 5-year incidence of advanced age-related macular degeneration (inter-eye kappa = 0.23) with AUC of 0.72. The 95% CI from the naïve approach was slightly narrower (0.645, 0.794) than from the nonparametric (0.641, 0.797) or cluster bootstrap (0.641, 0.793) approaches. In an analysis of 1542 eyes (771 infants), birthweight and gestational age predicted treatment-requiring retinopathy of prematurity (inter-eye kappa = 0.98) with AUC of 0.80. Furthermore, the 95% CI from the naïve approach was narrower (0.769, 0.835) than from the nonparametric (0.755, 0.848) or cluster bootstrap (0.755, 0.845) approaches. 95% CIs for AUC differences between different models were narrower in the naïve approach than the nonparametric or cluster bootstrap approaches. Conclusion In ROC analysis of correlated eye data, ignoring inter-eye correlation leads to narrower 95% CI with underestimation dependent on magnitude of inter-eye correlation. Nonparametric and cluster bootstrap approaches properly account for inter-eye correlation.

Interpreting Retinal Nerve Fiber Layer Reflectance Defects Based on Presence of Retinal Nerve Fiber Bundles.

SIGNIFICANCEAdaptive-optics scanning-laser-ophthalmoscopy (AOSLO) retinal imaging of the retinal nerve fiber layer (RNFL) helps predict the severity of perimetric damage based on absence of fibers and projection of the defects in en face images of the RNFL from spectral-domain optical coherence tomography (SD-OCT).PURPOSEEn face images of the RNFL reveal reflectance defects in patients with glaucoma and predict locations of perimetric defects. These defects could arise from either loss of retinal nerve fiber bundles or reduced bundle reflectance. This study used AOSLO to assess presence of bundles in areas with RNFL reflectance defects on SD-OCT.METHODSAdaptive-optics scanning laser ophthalmoscopy was used to image a vertical strip of RNFL measuring approximately 30 × 3° between the optic disc and the fovea. Fifteen patients with glaucoma who had SD-OCT reflectance defects that passed through this region were chosen. Four patients had reflectance defects in both superior and inferior hemifields, so presence of bundles on AOSLO was assessed for 19 hemifields. Where bundles were present, the hemifield was scored for whether bundles seemed unusual (low contrast and/or low density). Perimetric defects were considered deep when sensitivity was below 15 dB.RESULTSTen hemifields had a region with no fibers present on AOSLO; all had a corresponding deep perimetric defect. The other nine hemifields had no region in the AOSLO image without fibers: four with normal fibers and five with unusual fibers. The only one of these nine hemifields with a deep perimetric defect was one with low-contrast fibers and overall thin RNFL.CONCLUSIONSRetinal nerve fiber layer reflectance defects, which were associated with deep perimetric defects, usually had a region with absence of fibers on AOSLO images of RNFL. Ability to predict severity of perimetric damage from en face SD-OCT RNFL reflectance images could benefit from quantification that differentiated between absence of fibers and unusual fibers.

Strategies to Improve Convolutional Neural Network Generalizability and Reference Standards for Glaucoma Detection From OCT Scans.

PurposeTo develop and evaluate methods to improve the generalizability of convolutional neural networks (CNNs) trained to detect glaucoma from optical coherence tomography retinal nerve fiber layer probability maps, as well as optical coherence tomography circumpapillary disc (circle) b-scans, and to explore impact of reference standard (RS) on CNN accuracy.MethodsCNNs previously optimized for glaucoma detection from retinal nerve fiber layer probability maps, and newly developed CNNs adapted for glaucoma detection from optical coherence tomography b-scans, were evaluated on an unseen dataset (i.e., data collected at a different site). Multiple techniques were used to enhance CNN generalizability, including augmenting the training dataset, using multimodal input, and training with confidently rated images. Model performance was evaluated with different RS.ResultsTraining with data augmentation and training on confident images enhanced the accuracy of the CNNs for glaucoma detection on a new dataset by 5% to 9%. CNN performance was optimal when a similar RS was used to establish labels both for the training and the testing sets. However, interestingly, the CNNs described here were robust to variation in the RS.ConclusionsCNN generalizability can be improved with data augmentation, multiple input image modalities, and training on images with confident ratings. CNNs trained and tested with the same RS achieved best accuracy, suggesting that choosing a thorough and consistent RS for training and testing improves generalization to new datasets.Translational RelevanceStrategies for enhancing CNN generalizability and for choosing optimal RS should be standard practice for CNNs before their deployment for glaucoma detection.

Impact of Artifacts From Optical Coherence Tomography Retinal Nerve Fiber Layer and Macula Scans on Detection of Glaucoma Progression

To determine the prevalence of artifacts on segmented spectral-domain optical coherence tomography (SDOCT) images and assess their impact on the interpretation of glaucomatous progression in the retinal nerve fiber layer (RNFL) profile and macular thickness map. Retrospective reliability analysis. Retrospective review of glaucoma and glaucoma suspect eyes imaged with SDOCT during a 1-month period. All cases had at least 4 sets of RNFL and macular images at 6-month intervals. SDOCT raw B-scans were examined to determine true progression and whether artifacts impacted the original interpretation of progression based on auto-segmented change maps. The co-prevalence of artifacts in the RNFL and macula was assessed, as well as the association of clinical factors with the likelihood of artifacts. A total of 190 eyes with 760 sets of OCT RNFL and macular scans were included. Fifty percent (96/190) of eyes had artifacts, either in the circumpapillary RNFL (83/190; 43.68%) or the macula (57/190; 30.0%). Epiretinal membrane and vitreomacular traction were the most common artifacts. True progression was present on 39.5% (75/190) of scans overall. Among scans with artifacts, 23.9% (23/96) of artifacts masked true progression (ie, false-negative), 36.5% (35/96) led to an interpretation of false progression (ie, false-positive), and 39.6% (38/96) had no effect on the interpretation of progression. The presence of true progression on the RNFL scan was significantly associated with the presence of true progression on the macular scan (P < .001). Similarly, the presence of artifacts on the RNFL scan was significantly associated with artifacts on the macular scan (P < .001). In multivariable analysis, severe glaucoma, hypertension, and age were significantly associated with the presence of artifacts on RNFL (P< .05). Artifacts are highly prevalent on both circumpapillary RNFL and macular scans on SDOCT images acquired in a glaucoma clinic. Artifacts can lead to false-positive and false-negative interpretation of progression when using only the auto-segmentation change maps. Thus, careful examination of the raw B-scan images of both the RNFL and macula is critical to identify artifacts and true glaucoma progression.

Reliability and Recommended Settings for Pediatric Circumpapillary Retinal Nerve Fiber Layer Imaging Using Hand-Held Optical Coherence Tomography.

PurposeTo investigate feasibility and reliability of 3-dimensional full circumpapillary retinal nerve fiber layer (cpRNFL) analysis in children, with and without glaucoma, without the use of sedation and to recommend a protocol for hand-held optical coherence tomography use.MethodsA cohort of pediatric glaucoma patients and normal children were imaged with hand-held optical coherence tomography to assess the feasibility of obtaining full cpRNFL. Two consecutive scans were acquired in a smaller sample to investigate test–retest repeatability and interassessor reproducibility. The cpRNFL thickness was assessed in four quadrants, at several visual angles from the optic nerve center.ResultsScanning was attempted in both eyes of 90 children with pediatric glaucoma and 180 controls to investigate feasibility (mean age, 6.98 ± 4.42 years). Scanning was not possible in 68 eyes of glaucoma children mainly owing to nystagmus, unclear optical media, or high refractive errors. Where three-dimensional imaging was possible, success at obtaining full cpRNFL was 67% in children with glaucoma and 89% for controls. Seventeen children with pediatric glaucoma and 34 controls contributed to reliability analysis (mean age, 6.3 ± 3.63 years). For repeatability intraclass correlation coefficients across quadrants ranged from 0.63 to 0.82 at 4° and improved to 0.88 to 0.94 at 6°. Intraclass correlation coefficients for reproducibility were also highest at 6° (>0.97 across all quadrants).ConclusionsWe demonstrate that acquisition and measurement of cpRNFL thickness values using 3-dimensional hand-held optical coherence tomography volumes in awake children is both feasible and reliable and is optimal at 6° from optic nerve center.Translational RelevanceOur recommended protocol provides guidance on how pediatric optic nerve pathologies are managed by clinicians.