OCT Retinal Nerve Fiber Layer Research Articles

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.

SAkuraBONSAI: Protocol design of a novel, prospective study to explore clinical, imaging, and biomarker outcomes in patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorder receiving open-label satralizumab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD. SAkuraBONSAI will evaluate clinical disease activity measures, patient-reported outcomes (PROs), pharmacokinetics, and safety of satralizumab in AQP4-IgG+ NMOSD. Correlations between imaging markers (magnetic resonance imaging [MRI] and optical coherence tomography [OCT]) and blood and cerebrospinal fluid (CSF) biomarkers will be investigated. SAkuraBONSAI is a prospective, open-label, multicenter, international, Phase 4 study that will enroll approximately 100 adults (18-74 years) with AQP4-IgG+ NMOSD. This study includes two patient cohorts: newly diagnosed, treatment-naïve patients (Cohort 1; n = 60); and inadequate responders to recent (<6 months) rituximab infusion (Cohort 2; n = 40). Satralizumab monotherapy (120 mg) will be administered subcutaneously at Weeks 0, 2, 4, and Q4W thereafter for a total of 92 weeks. Disease activity related to relapses (proportion relapse-free, annualized relapse rate, time to relapse, and relapse severity), disability progression (Expanded Disability Status Scale), cognition (Symbol Digit Modalities Test), and ophthalmological changes (visual acuity; National Eye Institute Visual Function Questionnaire-25) will all be assessed. Peri-papillary retinal nerve fiber layer and ganglion cell complex thickness will be monitored using advanced OCT (retinal nerve fiber layer and ganglion cell plus inner plexiform layer thickness). Lesion activity and atrophy will be monitored by MRI. Pharmacokinetics, PROs, and blood and CSF mechanistic biomarkers will be assessed regularly. Safety outcomes include the incidence and severity of adverse events. SAkuraBONSAI will incorporate comprehensive imaging, fluid biomarker, and clinical assessments in patients with AQP4-IgG+ NMOSD. SAkuraBONSAI will provide new insights into the mechanism of action of satralizumab in NMOSD, while offering the opportunity to identify clinically relevant neurological, immunological, and imaging markers.

Vitreous Hemorrhage from Papilledema After Neck Massage

A 41-year-old woman presented with left eye floaters after receiving a head and neck massage while prone. The patient had a history of idiopathic intracranial hypertension, treated with acetazolamide. Examination revealed a left inferior optic disc hemorrhage and bilateral optic disc edema (A-B). OCT of the left optic nerve depicted retinal nerve fiber edema with hyperreflectivity in the preretinal space extending into the vitreous (C). OCT retinal nerve fiber layer confirmed bilateral disc edema (D). This case represents active disc hemorrhage observed on OCT imaging secondary to idiopathic intracranial hypertension and exacerbated by pressure from massage, which induced venous rupture on the optic disc (Magnified version of Figure A-D is available online at www.aaojournal.org).

Circular Contrast Perimetry via Web Application: A Patient Appraisal and Comparison to Standard Automated Perimetry.

PurposeThe purpose of the study was to compare a novel, 24°, 52-locus online circular contrast perimetry (OCCP) application against standard automated perimetry (SAP) in terms of both diagnostic accuracy and patient attitudes.DesignThis was a cross-sectional study.SubjectsNinety-five participants (42 controls and 53 open-angle glaucoma patients) were included.MethodsParticipants performed both perimetry tests and then completed an online survey. Subjective feedback responses were collected.Main Outcome MeasuresAgreement, sensitivity, specificity, and area under receiver operating curves (AUCs) were compared for the parameters of OCCP, SAP, and OCT for the retinal nerve fiber layer (RNFL) and macular ganglion cell complex inner plexiform layer (GCC + IPL). Participant attitudes toward the OCCP test versus the SAP test, in both glaucoma patients and controls, were compared. Rasch analysis assessed the psychometric properties of the survey and intergroup variability.ResultsThe AUC for OCCP mean deviation (MD) was 0.959 ± 0.02. Compared with other instruments’ parameters with the highest AUC, it was superior to SAP MD (0.871 ± 0.04, P = 0.03) and OCT GCC + IPL (0.871 ± 0.04, P = 0.03) and similar to OCT RNFL inferior thickness (IT) (0.917 ± 0.03, no significance). Online circular contrast perimetry pointwise sensitivity was less than SAP by 4.30 dB (95% confidence interval = 4.02–4.59); 95% limits of agreement ranged from −6.28 to −2.33 dB. At the best cutoff, the OCCP MD had a sensitivity of 98% and specificity of 85% for detecting glaucoma. Cohen's kappa demonstrated good agreement with SAP MD (0.69) and OCT RNFL IT (0.62) and moderate agreement with OCT GCC + IPL IT (0.57). Participants preferred OCCP across most survey parameters (P < 0.0001). Rasch analysis demonstrated no differential item functioning for clinical group, gender, or age.ConclusionsWith similar diagnostic metrics to SAP, OCCP offers an improved user experience with the potential to increase the provision of care and improve disease surveillance outcomes.

Association Between Serum Vitamin D Level and Rates of Structural and Functional Glaucomatous Progression.

In a retrospective cohort study, serum vitamin D levels were not associated with rates of structural or functional loss in glaucoma patients, suggesting that low vitamin D level is not a risk factor for progression. To investigate the association between serum vitamin D level and rates of functional and structural glaucomatous loss over time. This study included 826 eyes of 536 glaucoma or suspect patients with an average follow-up of 4.8±1.9 years. All patients had at least 1 serum vitamin D measurement, and all eyes had at least 2 reliable standard automated perimetry (SAP) tests and 2 spectral-domain optical coherence tomography (SD OCT) tests with a minimum follow-up of 6 months. Multivariable linear mixed-effects models were used to estimate the association of vitamin D level with rates of change in SAP mean deviation (MD) and OCT retinal nerve fiber layer (RNFL) thickness over time while adjusting for potential confounding factors. Patients had an average of 3.4±1.7 SAP tests, 4.8±1.9 SD OCT tests, and 2.3±1.9 vitamin D measurements. The average serum vitamin D level was 33.9±13.2 ng/mL. Mean rates of MD and RNFL change were -0.03±0.08 dB/y and -0.68±0.64 µm/y, respectively. After controlling for confounding factors, there was no statistically significant association between mean vitamin D level and rates of MD (β=0.038, 95% CI: -0.006, 0.082, P =0.09) or RNFL loss over time (β=-0.018, 95% CI: -0.092, 0.055, P =0.62). We did not find a significant association between vitamin D level and rates of visual field or RNFL loss over time in individuals with glaucoma and glaucoma suspect patients.

The influence of mild posterior capsular opacification on spectral domain optical coherence tomography retinal nerve fiber layer thickness.

Τo investigate whether Yag laser capsulotomy, in addition to restoring ocular media transparency, may also significantly alter retinal nerve fiber layer (RNFL) thickness analysis and spectral domain optical coherence tomography (SD OCT) indices and quality parameters, such as signal strength (SS), in patients with mild, diffuse posterior capsular opacification (PCO). Prospective interventional case series study which enrolled 28 patients with mild PCO and good baseline best-corrected visual acuity (BCVA). All patients underwent a complete ophthalmologic examination, including SD OCT RNFL thickness measurement prior to Yag laser capsulotomy. Following laser intervention, all patients repeated the same complete ophthalmic examination and results were recorded and analysed. Mean RNFL thickness showed a significant postoperative increase from 89.6 to 94.1μm (p = 0.01), which was also confirmed for superior (p = 0.041), nasal (p = 0.011) and inferior quadrants (p = 0.032). SS and BCVA were also significantly increased after laser treatment (p < 0.01). A significant positive correlation was observed between SS and mean RNFL thickness postoperatively (p = 0.043) but not preoperatively (p = 0.059). Similarly, a significant relationship was found between BCVA and average RNFL thickness after (p = 0.017) but not before (p = 0.457) laser intervention. Our study suggests that the presence of even mild PCO may alter the sensitivity of SD-OCT acquisition and lead to inadvertent RNFL thickness underestimation. Clinicians should be alerted to this contingency and take it into consideration when evaluating various optic neuropathies with SD OCT, in pseudophakic eyes.

Multifocal visual evoked potential for evaluation of open-angle glaucoma.

To correlate multifocal visual evoked potential (mfVEP) findings with static automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) in eyes with primary open- angle glaucoma (POAG). This cross-sectional study included a consecutive sample of 40 eyes of 40 patients with POAG. The participants underwent a complete ophthalmologic assessment, axial length (AL) measurement, and assessments with SAP, SD-OCT, and mfVEP. POAG cases were aged 49.70 (14.16) years (mean [SD]) and most were females (n = 24, 60%). For eyes of patients with POAG, the mfVEP upper-ring signal-to-noise ratio (SNR) showed a significant negative correlation with best-corrected logMAR visual acuity (r = - 0.33; P = 0.038), and a significant positive correlation with the superior hemifield of the visual field (VF) and the inferior-quadrant retinal nerve fiber layer (RNFL) thickness (r = + 0.34; P = 0.030; r = + 0.51; P < 0.001, respectively). Similarly, the mfVEP lower-ring SNR showed a significant negative correlation with best-corrected logMAR visual acuity (r = - 0.36; P = 0.024) and a significant positive correlation with the inferior hemifield of the VF and superior quadrant RNFL thickness (r = + 0.55; P < 0.001 and r = + 0.70; P < 0.001, respectively). mfVEP is a promising tool for objective assessment of the VF in patients with POAG, as it is positively correlated with the VF and OCT RNFL thickness. Future longitudinal studies with a larger sample size and a specific glaucoma subtype, along with multiple follow-up evaluations, are warranted to confirm our preliminary results.

Deep Learning Image Analysis of Optical Coherence Tomography Angiography Measured Vessel Density Improves Classification of Healthy and Glaucoma Eyes

To compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes. Comparison of diagnostic approaches. A total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5×4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared. Adjusted AUPRCs for GBC models were 0.89 (95% CI=0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons). Deep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes.

Relationship of Peripapillary Retinal Perfusion with Peripapillary Retinal Nerve Fiber Layer Thickness in Diabetes Mellitus Patients without Diabetic Retinopathy

Introduction: Impaired blood flow is an early sign of retinal dysfunction in diabetes. Impaired blood flow of the radial peripapillary capillaries can affect the Retinal Nerve Fiber Layer (RNFL) or ganglion cell function. &#x0D; Methods: This was an analytic cross-sectional study in February-April 2019 at Bandung. The subjects of this study were 41 people (79 eyes) divided into two groups, group A (healthy subjects) 19 people (37 eyes) and group B (DM type 2 without diabetic retinopathy) 22 people (42 eyes). Peripapillary retinal perfusion was assesed using OCT Angiography and RNFL thickness was assesed using OCT. Pearson or Spearman correlation statistics test was used to analyze the result. P value ≤0.05 was consiedered significant.&#x0D; Results: There was a decrease in peripapillary retinal perfusion density in the inferior quadrant (P = 0.003) and flux index throughout the peripapillary retinal quadrant (P = 0.0001) but an increase in RNFL thickness in the peripapillary temporal quadrant (P = 0.012) compared to control grup. Positive correlation was found between peripapillary retinal perfusion density and RNFL thickness globally (r = 0.480, P = 0.001), superior quadrant (r = 0.436, P = 0.004), and inferior quadrant (r = 0.608, P = 0.000). A positive correlation was also found between the peripapillary flux and RNFL thickness globally (r = 0.517, P = 0.000), superior quadrant (r = 0.630, P = 0.000), and inferior quadrant (r = 0.519, P = 0.000).&#x0D; Conclusions: There was a relationship between peripapillary retinal perfusion and RNFL thickness in DM patients without diabetic retinopathy.&#x0D; Keywords: Peripapillary perfusion, RNFL thickness, Diabetes.

Earlier Detection of Glaucoma Progression Using High-Density 3-Dimensional Spectral-Domain OCT Optic Nerve Volume Scans

To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. Prospective, longitudinal cohort study. One hundred twenty-four eyes of 124 patients with open-angle glaucoma. Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test-retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. Time to glaucoma progression among all 4 methods. Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ= 0.095-0.300). High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).

Follow-Up of Nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography.

PurposeThe purpose of this study was to describe capillary changes in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography-angiography (OCT-A) and correlate the results with best corrected visual acuity (BCVA), visual field, OCT retinal nerve fiber layer (RNFL), and combined thickness of ganglion cell and inner plexiform layers (GCIPL) thicknesses.MethodsWe enrolled 22 eyes with acute NAION and 30 normal control (NC) subjects in this study. Whole en face image vessel density (WiVD) was measured in the radial peripapillary capillary plexus (RPC), superficial capillary plexus (SCP), and deep vascular complex (DVC) using OCT-A. The examination was repeated at 1 (M1), 3 (M3), 6 (M6), and 9 (M9) months after presentation for NAION.ResultsThe initial RPC WiVD was significantly reduced in the acute NAION group compared to the NC group (P < 0.0001). Over the course of NAION follow-up, RPC WiVD was significantly reduced at M1 (P < 0.001 compared to M0) and M3 (P < 0.0001 compared to M1). However, there was no significant further decrease at M6 and M9. The initial SCP WiVD was significantly reduced in the NAION group compared to the NC group (P < 0.0001 for both). Over the course of NAION follow-up, a significant decrease was observed for SCP WiVD at M1 (P < 0.001 compared to M0), but no significant change was seen at M3, M6, or M9. DVC was normal in the NAION group. Correlations were found between GCIPL and SCP WiVD in the NAION acute phase (R = 0.604, P = 0.003) and in the M9 atrophic stage (R = 0.551, P = 0.009). At M9, RPC WiVD was correlated with BCVA (R = −0.562, P = 0.007), mean deviation (R = 0.518, P = 0.01), and RNFL (R = 0.655, P = 0.001).ConclusionsOver the course of NAION, OCT-A provided detailed visualization of retinal capillary plexus involvement.

Effect of Diabetes Control on Rates of Structural and Functional Loss in Patients with Glaucoma

To investigate the association between levels of diabetes mellitus (DM) control and rates of visual field and retinal nerve fiber layer (RNFL) loss over time in glaucoma. Retrospective cohort study. A total of 351 eyes of 222 patients with type 2 DM with concomitant primary open-angle glaucoma (POAG) or suspected glaucoma extracted from the Duke Glaucoma Registry. All patients had at least 2 reliable standard automated perimetry (SAP) tests, 2 spectral domain OCT (SD-OCT) tests, and 2 glycated hemoglobin (HbA1c) measures over time with a minimum follow-up of 6 months. Values of HbA1c were summarized for each patient as mean, peak, and fluctuation across time. Multivariable linear mixed models were used to estimate the effect of HbA1c on rates of change in SAP mean deviation (MD) and OCT RNFL thickness loss over time while adjusting for various confounding factors. Rates of change in MD and RNFL thickness over time. Subjects had a mean baseline age of 62.5 ± 10.2 years and follow-up time of 6.9 ± 5.1 years. Subjects had an average of 4.8 SAP tests (range, 2-28), 3.6 SD-OCT tests (range, 2-10), and 8.3 HbA1c tests (range, 2-21). Average HbA1c mean was 7.1% ± 1.1% (range, 5.4-11.7), peak HbA1c over time was 8.1% ± 2% (range, 5.5-15.6), and HbA1c fluctuation was 0.6% ± 0.6% (range, 0-4.4). Mean rate of SAP MD changewas-0.09 ± 0.20 decibel/year(median -0.06 decibel/year; interquartile range -0.15 to 0.01 decibel/year), and mean rate of RNFL change was-0.83 ± 0.51 μm/year(median -0.76 μm/year; interquartile range -1.06 to 0.56 μm/year). After adjustment for confounding factors, mean, peak, and fluctuation in HbA1c levels were not significantly associated with rates of MD change over time (P= 0.994, P= 0.689, P= 0.920, respectively), nor were rates of change in RNFL loss over time (P= 0.805, P= 0.575, P= 0.770). We did not find a significant association between diabetes control, as measured by levels of HbA1c, and rates of visual field or RNFL loss over time in individuals with glaucoma or suspected glaucoma.

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.

Detection of Progressive Glaucomatous Optic Nerve Damage on Fundus Photographs with Deep Learning

PurposeTo investigate whether predictions of retinal nerve fiber layer (RNFL) thickness obtained from a deep learning model applied to fundus photographs can detect progressive glaucomatous changes over time.DesignRetrospective cohort study.ParticipantsEighty-six thousand one hundred twenty-three pairs of color fundus photographs and spectral-domain (SD) OCT images collected during 21 232 visits from 8831 eyes of 5529 patients with glaucoma or glaucoma suspects.MethodsA deep learning convolutional neural network was trained to assess fundus photographs and to predict SD OCT global RNFL thickness measurements. The model then was tested on an independent sample of eyes that had longitudinal follow-up with both fundus photography and SD OCT. The ability to detect eyes that had statistically significant slopes of SD OCT change was assessed by receiver operating characteristic (ROC) curves. The repeatability of RNFL thickness predictions was investigated by measurements obtained from multiple photographs that had been acquired during the same day.Main Outcome MeasuresThe relationship between change in predicted RNFL thickness from photographs and change in SD OCT RNFL thickness over time.ResultsThe test sample consisted of 33 466 pairs of fundus photographs and SD OCT images collected during 7125 visits from 1147 eyes of 717 patients. Eyes in the test sample were followed up for an average of 5.3 ± 3.3 years, with an average of 6.2 ± 3.8 visits. A significant correlation was found between change over time in predicted and observed RNFL thickness (r = 0.76; 95% confidence interval [CI], 0.70–0.80; P < 0.001). Retinal nerve fiber layer predictions showed an ROC curve area of 0.86 (95% CI, 0.83–0.88) to discriminate progressors from nonprogressors. For detecting fast progressors (slope faster than 2 μm/year), the ROC curve area was 0.96 (95% CI, 0.94–0.98), with a sensitivity of 97% for 80% specificity and 85% for 90% specificity. For photographs obtained at the same visit, the intraclass correlation coefficient was 0.946 (95% CI, 0.940–0.952), with a coefficient of variation of 3.2% (95% CI, 3.1%–3.3%).ConclusionsA deep learning model was able to obtain objective and quantitative estimates of RNFL thickness that correlated well with SD OCT measurements and potentially could be used to monitor for glaucomatous changes over time.

Impact of Intraocular Pressure Control on Rates of Retinal Nerve Fiber Layer Loss in a Large Clinical Population

To investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population. Retrospective cohort study. A total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients. Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than-1.0 μm/year; moderate if between-1.0 and-2.0 μm/year; and fast if faster than-2.0 μm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. Rates of change in SD-OCT RNFL thickness according to levels of IOP control. Eyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was-0.68±0.59 μm/year. Each 1 mmHg higher mean IOP was associated with 0.05 μm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg. Intraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice.

The Trajectory of Glaucoma Progression in 2-Dimensional Structural–Functional Space

To present a method that allows visualization of functional and structural change in 2-dimensional space. Retrospective, longitudinal, observational study. Patients from the Stein Eye Institute, UCLA from 1993 through2017. Patients were arranged into 2 cohorts. Cohort 1 was used to create a structural score for the horizontal axis of the structural-functional (S-F) 2-dimensional space. The visual field (VF) index was used for the vertical axis as the functional score. Cohort 2 was used to apply those scores for analysis of S-F progression with a combined vector. The first cohort included eyes with mild glaucoma (abnormal glaucoma hemifield test results, pattern standard deviation <0.05 on 2 examinations, or mean deviation [MD] >-5 dB) and normal control participants. The second cohort included all stages of open-angle glaucoma with ≥5 OCT retinal nerve fiber layer scans, ≥5 reliable visual field (VF) results, and follow-up of ≥4 years. Vectors were created for each eye to represent the trajectory of glaucoma progression over time. Each vector was defined by structural (x-axis) and functional (y-axis) components. The structural component was calculated with a linear model of Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) scores over time. The functional component was calculated with a linear model of VF measurements over time. The resultant vector and its confidence interval were plotted in 2-dimensional S-F space. Eyes were divided into severity stages based on baseline MD. A mean vector was calculated for each severity stage. We obtained 290 vectors from 290 eyes of 196 patients. The mean ± standard deviation follow-up period was 14.6±3.1 years. Average age was 58.6±8.8 years. Preperimetric, mild, moderate, and severe categories included 41, 89, 97, and 63 eyes, respectively. Mean baseline MDs were 0.8 dB, -0.95 dB, -3.57 dB, and -11.51 dB, respectively, and mean vector slopes for each severity categories were 0.79, 0.95, 1.95, and 2.08, respectively. Cook's distance removed 131 (7.1%) and 137 (7.4%) outliers from the structure and function regressions, respectively. We report a method to visualize the trajectory of a patient's glaucoma progression in a 2-dimensional S-F space. The slope of the trajectory of glaucoma progression is a function of the severity of the disease.

Correlation Between Optic Disc Peripapillary Capillary Network and Papilledema Grading in Patients With Idiopathic Intracranial Hypertension: A Study of Optical Coherence Tomography Angiography.

The continued increase in idiopathic intracranial hypertension (IIH) prevalence has many implications for societal health care. Its potential vision-threatening consequences make ophthalmologists key players in its diagnosis and management. Newer technology such as optical coherence tomography angiography (OCT-A) enables evaluation of the branching complexity of the peripapillary capillary plexus, a region where accurate imaging via fluorescein angiography was previously limited. A cross-sectional, observational study of 23 (46 eyes) consecutive patients with IIH. Peripapillary total vasculature was recorded using commercial OCT-A en face vessel density mapping. In addition, OCT-A blood flow slab was compared with papilledema grading. OCT-A images were analyzed using a customized image analysis protocol using ImageJ software (v1.51w) and Photoshop software (Adobe Systems, CA). SPSS software version 25 was used for statistical analysis (SPSS Inc, IBM, Chicago, IL). Skeletonized vessel density peripapillary capillary plexus was significantly associated with Frisen papilledema grades, OCT retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness with a P < 0.001, P = 0.022, and P = 0.006, respectively. Every point increase in grade was correlated with a decrease of 9.1 pixels/mm2 in vessel density (R = 0.512, β = -0.115 ± 0.029; P < 0.001). Increased papilledema was correlated with an increased retinal blood flow percentage (R = 0.300, β = 2.114 ± 1.013; P < 0.05) and decreased choroidal blood flow (CBF) percentage (R = 0.300, β = 2.114 ± 1.013; P < 0.05). Every point increase in grade was correlated with a decrease in CBF by 47.4%, as calculated using a linear best-fit line inclusive for all of the data points. OCT-A allows for effective visualization and quantification of the peripapillary retinal vasculature. Our results demonstrate a correlation between skeletonized peripapillary density and papilledema grading, OCT RNFL thickness, and GCL thickness. In addition, we show a significant negative correlation between CBF and papilledema grading. These changes provide key findings regarding the pathophysiology of optic neuropathy in papilledema and highlight the potential of OCT-A as a diagnostic tool for papilledema and a clinical marker for detecting early optic nerve damage.

Influence of Choroidal Microvasculature Dropout on the Rate of Glaucomatous Progression: A Prospective Study

To determine the prognostic significance of choroidal microvasculature dropout (MvD) to predict the future rate of progressive retinal nerve fiber layer (RNFL) thinning in eyes with primary open-angle glaucoma (POAG). Prospective, longitudinal case series. This study enrolled 101 eyes of 101 patients with POAG who underwent OCT angiography (OCTA) imaging of the optic nerve head at baseline and were followed up for at least 2 years thereafter, during which RNFL thickness was measured by serial spectral-domain OCT. The peripapillary microvasculature was evaluated by examining en face OCTA images. Choroidal MvD was defined as a focal sectoral capillary dropout with no visible microvascular network in the choroidal layer. The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements. Influence of the presence of an MvD on the rate of subsequent RNFL thinning. Microvasculature dropout was identified in 48 eyes (47.5%). The rate of global RNFL thinning was significantly faster in eyes with MvD than eyes without MvD (-1.6±0.8 vs.-1.2±0.9 μm/year, P= 0.018). Eyes with MvD in the inferior hemisphere (n= 41) showed a faster rate of inferior RNFL thinning than eyes without MvD (P= 0.036). Eyes with MvD in both the superior and inferior hemispheres (n= 5) showed faster rates of superior (P= 0.027) and inferior (P= 0.016) RNFL thinning than eyes without MvD. Multivariate regression analysis showed that MvD at baseline (P= 0.003) and the presence of disc hemorrhage during follow-up (P= 0.001) were independently associated with a faster rate of global RNFL thinning. Microvasculature dropout was an independent predictor of a faster rate of progressive RNFL thinning in patients with POAG. Microvasculature dropout location was topographically associated with the location of faster RNFL thinning.

Deep Learning Approaches Predict Glaucomatous Visual Field Damage from OCT Optic Nerve Head En Face Images and Retinal Nerve Fiber Layer Thickness Maps

To develop and evaluate a deep learning system for differentiating between eyes with and without glaucomatous visual field damage (GVFD) and predicting the severity of GFVD from spectral domain OCT (SDOCT) optic nerve head images. Evaluation of a diagnostic technology. A total of 9765 visual field (VF) SD OCT pairs collected from 1194 participants with and without GVFD (1909 eyes). Deep learning models were trained to use SD OCT retinal nerve fiber layer (RNFL) thickness maps, RNFL en face images, and confocal scanning laser ophthalmoscopy (CSLO) images to identify eyes with GVFD and predict quantitative VF mean deviation (MD), pattern standard deviation (PSD), and mean VF sectoral pattern deviation (PD) from SD OCT data. Deep learning models were compared with mean RNFL thickness for identifying GVFD using area under the curve (AUC), sensitivity, and specificity. For predicting MD, PSD, and mean sectoral PD, models were evaluated using R2 and mean absolute error (MAE). In the independent test dataset, the deep learning models based on RNFL en face images achieved an AUC of 0.88 for identifying eyes with GVFD and 0.82 for detecting mild GVFD significantly (P < 0.001) better than using mean RNFL thickness measurements (AUC= 0.82 and 0.73, respectively). Deep learning models outperformed standard RNFL thickness measurements in predicting all quantitative VF metrics. In predicting MD, deep learning models based on RNFL en face images achieved an R2 of 0.70 and MAE of 2.5 decibels (dB) compared with 0.45 and 3.7 dB for RNFL thickness measurements. In predicting mean VF sectoral PD, deep learning models achieved high accuracy in the inferior nasal (R2= 0.60) and superior nasal (R2= 0.67) sectors, moderate accuracy in inferior (R2= 0.26) and superior (R2= 0.35) sectors, and lower accuracy in the central (R2=0.15) and temporal (R2= 0.12) sectors. Deep learning models had high accuracy in identifying eyes with GFVD and predicting theseverity of functional loss from SD OCT images. Accurately predicting the severity of GFVD from SD OCT imaging can help clinicians more effectively individualize the frequency of VF testing to the individual patient.