Prevalence of Diagnosed Ocular Disease in Veterans with Serious Mental Illness

Objective To compare the prevalence of diagnosed ocular disease and eye disease treatment between VA patients with and without serious mental illness (SMI). Methods Retrospective comparison of diagnosed ocular disease and treatment prevalence among patients with and without diagnosed SMI in fiscal year (FY) 2011 in the VA Capitol Health Care System (VISN 5). Results We identified 6,462 VA patients with SMI and 137,933 without SMI. The prevalence of diagnosed ocular disease was 22.7% in SMI patients and 35.4% in non-SMI patients (P <0.001). Those with serious mental illness had a higher prevalence of glaucoma (10.2% vs. 7.1% P < 0.0001), cataract (12.6% vs. 9.2% P < 0.0001), and dry eye (4.0% vs. 2.7% P < 0.0001). 34.3% of SMI subjects had been seen in ophthalmology or optometry vs. 23.0% of controls (P < 0.0001). Conclusion VA patients with SMI have a greater prevalence of diagnosed ocular disease, particularly cataract, glaucoma, and dry eye. While SMI patients utilize eye care services at a higher rate than the general VA population, the majority of subjects with serious mental illness do not get recommended annual eye examinations. More consistent annual ocular screening among VA patients with SMI may be indicated

MEMO: Dataset and Methods for Robust Multimodal Retinal Image Registration with Large or Small Vessel Density Differences

The measurement of retinal blood flow (RBF) in capillaries can provide a powerful biomarker for the early diagnosis and treatment of ocular diseases. However, no single modality can determine capillary flowrates with high precision. Combining erythrocyte-mediated angiography (EMA) with optical coherence tomography angiography (OCTA) has the potential to achieve this goal, as EMA can measure the absolute 2D RBF of retinal microvasculature and OCTA can provide the 3D structural images of capillaries. However, multimodal retinal image registration between these two modalities remains largely unexplored. To fill this gap, we establish MEMO, the first public multimodal EMA and OCTA retinal image dataset. A unique challenge in multimodal retinal image registration between these modalities is the relatively large difference in vessel density (VD). To address this challenge, we propose a segmentation-based deep-learning framework (VDD-Reg) and a new evaluation metric (MSD), which provide robust results despite differences in vessel density. VDD-Reg consists of a vessel segmentation module and a registration module. To train the vessel segmentation module, we further designed a two-stage semi-supervised learning framework (LVD-Seg) combining supervised and unsupervised losses. We demonstrate that VDD-Reg outperforms baseline methods quantitatively and qualitatively for cases of both small VD differences (using the CF-FA dataset) and large VD differences (using our MEMO dataset). Moreover, VDD-Reg requires as few as three annotated vessel segmentation masks to maintain its accuracy, demonstrating its feasibility.Comment: Submitted to IEEE JBH

An Artificial Intelligence Approach to Detect Visual Field Progression in Glaucoma Based on Spatial Pattern Analysis.

Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P \u3c 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns

Evidence of Neurovascular Water Exchange and Endothelial Vascular Dysfunction in Schizophrenia: An Exploratory Study

BACKGROUND AND HYPOTHESIS: Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood-brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD. STUDY DESIGN: We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = 32 SSD) is impaired in SSD and associated with clinical symptoms. Peripheral vascular endothelial health was examined by brachial artery flow-mediated dilation (n = 44 HC, n = 37 SSD) to examine whether centrally measured Kw is related to endothelial functions. STUDY RESULTS: Whole-brain average Kw was significantly reduced in SSD (P = .007). Exploratory analyses demonstrated neurovascular water exchange reductions in the right parietal lobe, including the supramarginal gyrus (P = .002) and postcentral gyrus (P = .008). Reduced right superior corona radiata (P = .001) and right angular gyrus Kw (P = .006) was associated with negative symptoms. Peripheral endothelial function was also significantly reduced in SSD (P = .0001). Kw in 94% of brain regions in HC positively associated with peripheral endothelial function, which was not observed in SSD, where the correlation was inversed in 52% of brain regions. CONCLUSIONS: This study provides initial evidence of neurovascular water exchange abnormalities, which appeared clinically associated, especially with negative symptoms, in schizophrenia

Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C&gt;G, p.(Pro989Arg); c.5235T&gt;G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles

OCTA in neurodegenerative optic neuropathies: emerging biomarkers at the eye-brain interface.

OCTA imaging in optic neuropathies

Repeatability and Comparability of Retinal Blood Vessel Caliber Measurements by OCTA

Background: To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). Methods: In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. Results: A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). Conclusions: Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels

Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C&gt;G, p.(Pro989Arg); c.5235T&gt;G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles