The ability of deep learning architectures to identify glaucomatous optic neuropathy (GON) in fundus photographs was evaluated. A large database of fundus photographs (n = 14,822) from a racially and ...ethnically diverse group of individuals (over 33% of African descent) was evaluated by expert reviewers and classified as GON or healthy. Several deep learning architectures and the impact of transfer learning were evaluated. The best performing model achieved an overall area under receiver operating characteristic (AUC) of 0.91 in distinguishing GON eyes from healthy eyes. It also achieved an AUC of 0.97 for identifying GON eyes with moderate-to-severe functional loss and 0.89 for GON eyes with mild functional loss. A sensitivity of 88% at a set 95% specificity was achieved in detecting moderate-to-severe GON. In all cases, transfer improved performance and reduced training time. Model visualizations indicate that these deep learning models relied on, in part, anatomical features in the inferior and superior regions of the optic disc, areas commonly used by clinicians to diagnose GON. The results suggest that deep learning-based assessment of fundus images could be useful in clinical decision support systems and in the automation of large-scale glaucoma detection and screening programs.
To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes.
Prospective, ...longitudinal study.
One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes.
OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm
GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated.
The rates of GCC thinning and macular vessel density loss.
Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 -8.36, -5.88%/year) was significantly faster than GCC thinning (-2.13 -3.35, -0.90%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease.
Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.
The ventral tegmental area (VTA) plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity ...in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA.
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•Dopamine, GABA, and glutamate VTA neurons receive qualitatively similar inputs•Hypothalamus and raphe provide the largest inputs to each VTA cell type•Dopamine neurons receive proportionally more input from basal ganglia•Glutamate neurons receive more cortical inputs
Afferents to ventral tegmental area (VTA) neurons control reward-seeking behaviors, but their relative arrangement onto heterogeneous VTA cell types has remained largely unknown. Faget et al. now use an optimized transsynaptic retrograde tracing approach to provide a comprehensive map of inputs to each transmitter-defined VTA cell type.
Objective To evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). Study design This ...is a retrospective cohort study of infants intubated during the first 4 days after birth. Infants had birth weights (BWs) less than 1500 g and were admitted to the neonatal intensive care unit (NICU) at the University of California, San Diego, between January 1, 2005, and July 30, 2009. A subgroup analysis was done for infants with BW less than 750 g. Results A total of 308 infants with BW <1500 g, including 102 with a BW <750 g, were intubated within the first 4 days of life. The number of intubation attempts was significantly greater in infants with a BW <750 g who had severe IVH compared with those with mild or no IVH (OR 1.395, 95% CI 1.090-1.786, P = .008). For infants with BW <1500 g, the number of intubation attempts in the delivery room was significantly greater for infants with severe IVH (OR 1.317, 95% CI 1.052-1.649, P = .016). Conclusion Increased intubation attempts were associated with increased incidence of severe IVH in infants with BW less than 750 g and in infants less than 1500 g who were intubated only in the delivery room. Prospective studies are needed to further evaluate the relationship between intubation attempts and severe IVH.
To determine if OCT angiography (OCTA)-derived vessel density measurements can extend the available dynamic range for detecting glaucoma compared with spectral-domain (SD) OCT-derived thickness ...measurements.
Observational, cross-sectional study.
A total of 509 eyes from 38 healthy participants, 63 glaucoma suspects, and 193 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study.
Relative vessel density and tissue thickness measurement floors of perifoveal vessel density (pfVD), circumpapillary capillary density (cpCD), circumpapillary retinal nerve fiber (cpRNFL) thickness, ganglion cell complex (GCC) thickness, and visual field (VF) mean deviation (MD) were investigated and compared with a previously reported linear change point model (CPM) and locally weighted scatterplot smoothing curves.
Estimated vessel density and tissue thickness measurement floors and corresponding dynamic ranges.
Visual field MD ranged from -30.1 to 2.8 decibels (dB). No measurement floor was found for pfVD, which continued to decrease constantly until very advanced disease. A true floor (i.e., slope of approximately 0 after observed CPM change point) was detected for cpRNFL thickness only. The post-CPM estimated floors were 49.5±2.6 μm for cpRNFL thickness, 70.7±1.0 μm for GCC thickness, and 31.2±1.1% for cpCD. Perifoveal vessel density reached the post-CPM estimated floor later in the disease (VF MD, -25.8±3.8 dB) than cpCD (VF MD, -19.3±2.4 dB), cpRNFL thickness (VF MD, -17.5±3.3 dB), and GCC thickness (VF MD, -13.9±1.8 dB; P < 0.001). The number of available measurement steps from normal values to the CPM estimated floor was greatest for cpRNFL thickness (8.9), followed by GCC thickness (7.4), cpCD (4.5), and pfVD (3.8).
In late-stage glaucoma, particularly when VF MD is worse than -14 dB, OCTA-measured pfVD is a promising tool for monitoring progression because it does not have a detectable measurement floor. However, the number of steps within the dynamic range of a parameter also needs to be considered. Although thickness parameters reached the floor earlier than OCTA-measured pfVD, there are more such steps with thickness than OCTA parameters.
We conducted a cohort study on the impact of obesity on disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) measures in the inflammatory bowel disease (IBD) ...Partners cohort.
We performed a cross-sectional and longitudinal study within IBD Partners, an internet-based cohort of >15,000 patients living with Crohn's disease (CD) and ulcerative colitis (UC). We included adult patients with IBD, with recorded body mass index (BMI), with at least 6 months of follow-up, excluding patients with BMI < 18.5 kg/m. We evaluated the independent effect of World Health Organization classes of obesity on risk of clinical relapse or persistent disease activity (using validated disease activity indexes) and PROMIS measures, using multivariate logistic regression and linear regression, respectively.
We included 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC with intact colon, 20.3% obese). Obesity was independently, and in a dose-dependent fashion, associated with an increased risk of persistent disease activity or relapse in both patients with CD (class II or III obesity vs normal BMI: adjusted odds ratio, 1.86; 95% confidence interval, 1.30-2.68) and UC (adjusted odds ratio, 2.97; 95% confidence interval, 1.75-5.17). Obesity was also independently associated with higher anxiety, depression, fatigue, pain, and inferior social function scores in patients with CD and UC at baseline and with worsening depression, fatigue, pain, and social function in patients with CD on longitudinal assessment.
Obesity at baseline is independently associated with worsening disease activity and PROMIS measures in patients with IBD.
To evaluate the association of macular superficial vessel density (SVD) and projection-resolved deep vessel density (DVD) with past visual field (VF) progression in patients with primary open-angle ...glaucoma.
Retrospective cohort.
In this longitudinal study, 208 eyes of 147 patients with glaucoma from the Diagnostics Innovations in Glaucoma Study were included. Eligible participants were required to have at least five 24-2 VF tests over a minimum follow-up period of 3 years before macular optical coherence tomography angiography imaging. VF progression was defined based on both event-based pointwise linear regression and trend-based methods. The association of macular SVD and DVD with the probability and rate of past VF progression was evaluated using a linear mixed effects model.
Fifty-two (25%) eyes had VF progression based on the pointwise linear regression based criterion at the end of a mean ± standard deviation follow-up duration of 6.9 ± 1.2 years. In the event-based multivariable analysis, a lower baseline SVD was associated with a higher likelihood of past VF progression (odds ratio per 1% lower. 1.28; 95% confidence interval, 1.02–1.59). Similarly, in the trend-based multivariable analysis, lower macular SVD was associated with a faster past rate of mean deviation decline (coefficient = –0.03 dB/year; 95% confidence interval, –0.04 to –0.01). Event-based and trend-based analyses found no significant associations for macular DVD with the likelihood/rate of past VF progression (P > .05).
Lower macular SVD, and not DVD, was associated with a higher probability of past VF progression. Macular optical coherence tomography angiography imaging shows promise for identifying eyes at risk of VF progression in patients with glaucoma.
To compare standard reliability metrics and gaze tracking (GT) metrics on the Humphrey field analyzer (HFA).
Retrospective cross-sectional study.
The study was performed at the VA Medical Center, San ...Diego, and included 494 glaucoma and glaucoma suspect patients who had an HFA 24-2 SITA Fast visual field (VF) performed in both eyes. Standard reliability metrics (fixation loss FL, false-positive FP, and false-negative FN) were compared to GT metrics (deviations of 1°-2° M1, deviations of 3°-5° M3, deviations >6° M6, and tracking failure frequency TFF). The main outcome measures were Spearman rank-based correlation coefficient and area under the receiver operating characteristic (AUROC) curves between standard and GT reliability metrics.
The 95th percentile limits for GT metrics were 66.7% for M1, 67.5% for M3, 49.5% for M6, and 79.8% for TFF. There were statistically significant correlations between standard and GT reliability metrics using the 95th percentile as a binary cutoff for GT metrics. However, low Spearman correlation values and AUROC calculations suggest little clinical significance of the associations. FN increased as VF severity worsened (P < .001). M6 was lower in eyes with mild compared to moderate and advanced VF loss (P = .012).
GT metrics do not have a clinically significant association with standard reliability metrics. Both FN and M6 are influenced by VF severity. Aggregate GT metrics do not aid in reliability assessment. These findings suggest that GT metrics may provide an alternative or complementary measure of VF reliability.
This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non ...(n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.
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