Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy.

PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.

Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature.

BACKGROUND: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. METHODS: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases-based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. RESULTS: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). CONCLUSIONS: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6 mm and Montage 15 × 15 mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.

Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data.

PURPOSE: Despite widespread use of OCT, an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relationship to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Herein, we jointly analyzed OCT, electronic health record data, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiologic and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study. PARTICIPANTS: Forty-four thousand eight hundred twenty-three individuals from the UK Biobank (enrollment age range, 40-70 years; 54% women; median follow-up, 10 years). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age-squared (age2), sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD. RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, whereas retinal pigment epithelium (RPE) and Bruch's membrane (BM) complex thickening started after 57 years of age. Each standard deviation (SD) of PS thinning and RPE-BM complex thickening was associated with incident AMD (PS: hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.23-1.47; P = 3.7 × 10-11; RPE-BM complex: HR, 1.14; 95% CI, 1.06-1.22; P = 0.00024). The AMD PRS was associated with PS thinning (ß, -0.21 SD per twofold genetically increased risk of AMD; 95% CI, -0.23 to -0.19; P = 2.8 × 10-74), and its association with RPE-BM complex was U-shaped (thinning with AMD PRS less than the 92nd percentile and thickening with AMD PRS more than the 92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants Complement Factor H (CFH):rs570618-T, CFH:rs10922109-C, and Age-Related Maculopathy Susceptibility 2 (ARMS2)/High-Temperature Requirement Serine Protease 1 (HTRA1):rs3750846-C on PS thinning and SYN3/Tissue Inhibitor of Metalloprotease 3 (TIMP3):rs5754227-T on RPE-BM complex thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE-BM complex thickening by decades and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.

Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study.

PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.

A quantitative comparison of four optical coherence tomography angiography devices in healthy eyes.

PURPOSE: Optical coherence tomography angiography (OCT-A) is a novel imaging modality for the diagnosis of chorioretinal diseases. A number of FDA-approved OCT-A devices are currently commercially available, each with unique algorithms and scanning protocols. Although several published studies have compared different combinations of OCT-A machines, there is a lack of agreement on the consistency of measurements across OCT-A devices. Therefore, we conducted a prospective quantitative comparison of four available OCT-A platforms. METHODS: Subjects were scanned on four devices: Optovue RTVue-XR, Heidelberg Spectralis OCT2 module, Zeiss Plex Elite 9000 Swept-Source OCT, and Topcon DRI-OCT Triton Swept-Source OCT. 3 mm × 3 mm images were utilized for analysis. Foveal avascular zone (FAZ) area was separately and independently measured by two investigators. Fractal dimension (FD), superficial capillary plexus (SCP), and deep capillary plexus (DCP) vessel densities (VD) were calculated from binarized images using the Fiji image processing software. SCP and DCP VD were further calculated after images were skeletonized. Repeated measures ANOVA, post hoc tests, and interclass correlation coefficient (ICC) were performed for statistical analysis. RESULTS: Sixteen healthy eyes from sixteen patients were scanned on the four devices. Images of five eyes from the Triton device were excluded due to poor image quality; thus, the authors performed two sets comparisons, one with and one without the Triton machine. FAZ area showed no significant difference across devices with an ICC of > 95%. However, there were statistically significant differences for SCP and DCP VD both before and after skeletonization (p < 0.05). Fractal analysis revealed no significant difference of FD at the SCP; however, a statistically significant difference was found for FD at the DCP layer (p < 0.05). CONCLUSIONS: The results showed that FAZ measurements were consistent across all four devices, while significant differences in VD and FD measurements existed. Therefore, we suggest that for both clinical follow-up and research studies, FAZ area is a useful parameter for OCT-A image analysis when measurements are made on different machines, while VD and FD show significant variability when measured across devices.

The Impact of Psychiatric Disorder Diagnosis on Motivation to Quit and Stage of Change Among Patients at a Hospital-Based Outpatient Smoking Cessation Clinic.

OBJECTIVE: Smoking is among the greatest international public health concerns, causing excessive levels of preventable premature death, disability, and economic costs. The prevalence of tobacco use among people with psychiatric disorders (PDs) remains persistently high relative to the general population, highlighting the need to improve smoking cessation (SC) strategies in this group. We aimed to assess the associations between having a PD and baseline motivation to quit (MtQ) smoking and Prochaska's stage of change (SoC), two clinically important metrics linked to SC outcomes. Methods: This retrospective chart review included patients who completed a baseline visit at a hospital-based outpatient SC clinic (N = 896). Multivariate hierarchical logistic and linear regression models were developed to assess variables associated with MtQ (importance and confidence in quitting) and SoC, primarily PD category (externalizing, internalizing, externalizing/internalizing, psychotic or no PD) and secondarily, demographics, physical health history, and tobacco use/dependence metrics. Results: The variables negatively associated with MtQ were female sex (p = .011), older age (p = .038), deriving income from social assistance (p < .001), and age at smoking initiation (p = .005), whereas ≥ 1 quit attempt in the past year predicted higher MtQ (p < .0001). Being in the preparative/action SoC (versus the pre-contemplative/contemplative) was associated with income from social assistance (OR 0.39, p = .001), more daily cigarettes smoked (OR 0.98, p = .005) and ≥ 1 past-year quit attempt (OR 1.69, p = .013). Conclusions: Having a PD was not associated with either MtQ or SoC. Deriving income from social assistance predicted lower MtQ and SoC. Having made ≥ 1 quit attempt in the past year was associated with higher MtQ and SoC. Our study suggests that people with PDs are as motivated to quit smoking and ready for change as people without PDs, and smoking cessation efforts should be amplified in this group to address the disproportionately high level of tobacco use, especially because having at least one quit attempt may enhance MtQ and SoC.

FACTORS ASSOCIATED WITH THE USE OF 360-DEGREE LASER RETINOPEXY DURING PRIMARY VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE FOR RHEGMATOGENOUS RETINAL DETACHMENT AND IMPACT ON SURGICAL OUTCOMES (PRO STUDY REPORT NUMBER 4).

PURPOSE: To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS: This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS: Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION: Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

Cell communication by tunneling nanotubes: Implications in disease and therapeutic applications.

Intercellular communication is essential for the development and maintenance of multicellular organisms. Tunneling nanotubes (TNTs) are a recently recognized means of long and short distance communication between a wide variety of cell types. TNTs are transient filamentous membrane protrusions that connect cytoplasm of neighboring or distant cells. Cytoskeleton fiber-mediated transport of various cargoes occurs through these tubules. These cargoes range from small ions to whole organelles. TNTs have been shown to contribute not only to embryonic development and maintenance of homeostasis, but also to the spread of infectious particles and resistance to therapies. These functions in the development and progression of cancer and infectious disease have sparked increasing scrutiny of TNTs, as their contribution to disease progression lends them a promising therapeutic target. Herein, we summarize the current knowledge of TNT structure and formation as well as the role of TNTs in pathology, focusing on viral, prion, and malignant disease. We then discuss the therapeutic possibilities of TNTs in light of their varied functions. Despite recent progress in the growing field of TNT research, more studies are needed to precisely understand the role of TNTs in pathological conditions and to develop novel therapeutic strategies.

Myeloid sarcoma involving the greater wing of the sphenoid bone and additional skeletal sites presenting with unilateral proptosis and fevers.

We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.

Acute transient large-angle exotropia caused by traumatic orbital contusion.

We report an unusual case of acute large-angle left exotropia associated with blunt orbital trauma in a healthy 8-year-old boy. Examination revealed a large-angle left exotropia with limitation in adduction of the left eye. Microhyphema and commotio retinae of the left eye were also present. High-resolution orbital magnetic resonance imaging (MRI) demonstrated perimuscular and intramuscular edema mostly involving the left medial rectus muscle but also involving the left lateral rectus muscle. The extraocular muscle insertions were intact. Complete resolution of the strabismus and adduction limitation occurred within 24 hours of starting systemic steroid therapy. This case highlights the utility of high-resolution imaging to assess for injury to the extraocular muscles. If disinsertion, transection, or rupture of the muscle is not present on imaging, resolution may occur with systemic steroid therapy and surgical intervention is not needed.

Acute Zonal Occult Outer Retinopathy Associated With Retrobulbar Optic Neuritis.

A 17-year-old girl presented with unilateral retrobulbar optic neuritis as well as bilateral funduscopic findings and outer retinal dysfunction suggestive of acute zonal occult outer retinopathy (AZOOR). Fundus autofluorescence abnormalities, visual field loss, and electroretinographic changes were supportive of bilateral AZOOR. MRI was consistent with the diagnosis of clinically isolated syndrome (CIS), which is defined as a central nervous system demyelinating event that may herald the onset of multiple sclerosis (MS). While AZOOR previously has been linked to MS and demyelinating white matter lesions in the brain, our case seems unique due to concurrent development of AZOOR and retrobulbar optic neuritis as a CIS.

CFH Y402H polymorphism is associated with elevated vitreal GM-CSF and choroidal macrophages in the postmortem human eye.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people 50 years of age or older in developed countries. The homozygous CC genotype in the complement factor H (CFH) Y402H single nucleotide polymorphism (SNP; rs1061170) is widely recognized as a risk factor for the development of AMD. In this study, we examined vitreal levels of granulocyte macrophage colony-stimulating factor (GM-CSF), a hematopoietic cytokine, and macrophages in the choroid of postmortem human eyes genotyped for the CFH Y402H SNP. METHODS: Twenty-two pairs of postmortem, non-diseased, human donor eyes were obtained. The vitreous and retinal tissues of the left eyes were collected for GM-CSF level measurement and CFH Y402H genotyping, respectively. The right eyes were paraffin-embedded and sectioned for immunohistochemistry using a macrophage and microglia marker, CD68. Cell cultures of RPE cells were stimulated with complement C3a, C5a, 4-hydroxynonenal (HNE), or tumor necrosis factor alpha (TNF-α), and GM-CSF expression was measured with a suspension assay or quantitative PCR. RESULTS: Eyes genotyped with the CC or the CT risk variant of the CFH Y402H SNP showed significantly increased levels of GM-CSF in the vitreous compared to eyes with the protective TT variant (mean ± standard error of mean, 607.54±85.83 pg/ml or 656.32±15.20 pg/ml versus 286.69±81.96 pg/ml, p<0.05). The choroid of eye tissues genotyped with the CC variant showed higher levels of CD68 immunoreactivity than the tissues genotyped with the TT variant (p<0.05). The GM-CSF levels detected in the supernatant of RPE cells in culture treated with HNE or TNF-α were significantly higher compared to the non-treated control (145.88±5.06 pg/ml and 149.32±3.76 pg/ml versus 123.27±4.05 pg/ml, p<0.05). Furthermore, the gene expression of GM-CSF detected in the lysate of RPE cells stimulated with complement C3a or C5a showed significantly increased fold changes compared to the non-treated control (C3a: 2.38±0.31 fold, p<0.05; C5a: 2.84±0.54 fold, p<0.01). CONCLUSIONS: Our data showed a relationship between the CFH Y402H polymorphism and GM-CSF levels in the vitreous and accumulation of choroidal macrophages in the postmortem eye. These data suggest that the at-risk variant of the CFH gene may contribute to the dysregulation of proinflammatory cytokines locally in the eye.

Healthy young minds: the effects of a 1-hour classroom workshop on mental illness stigma in high school students.

This study aimed to test the effects of a 1-h classroom-based workshop, led by medical students, on mental illness stigma amongst secondary school students. Students (aged 14-17) from three public secondary schools in British Columbia participated in the workshop. A questionnaire measuring stigma (including stereotype endorsement and desire for social distance) was administered immediately before (T1), immediately after (T2), and 1-month after the workshop (T3). A total of 279 students met the study inclusion criteria. Total scores on the stigma scale decreased by 23 % between T1 and T2 (p < 0.01). This was sustained 1-month post-workshop with a 21 % stigma reduction compared to pre-intervention (p < 0.01). This effect was primarily due to improvements in scores that measured desire for social distance. There were no significant changes in scores that measured stereotype endorsement. Adolescents' stigmatizing attitudes can be effectively reduced through a 1-h easily implementable and cost-effective classroom-based workshop led by medical students.

Mitotic spindle assembly around RCC1-coated beads in Xenopus egg extracts.

During cell division the genetic material on chromosomes is distributed to daughter cells by a dynamic microtubule structure called the mitotic spindle. Here we establish a reconstitution system to assess the contribution of individual chromosome proteins to mitotic spindle formation around single 10 µm diameter porous glass beads in Xenopus egg extracts. We find that Regulator of Chromosome Condensation 1 (RCC1), the Guanine Nucleotide Exchange Factor (GEF) for the small GTPase Ran, can induce bipolar spindle formation. Remarkably, RCC1 beads oscillate within spindles from pole to pole, a behavior that could be converted to a more typical, stable association by the addition of a kinesin together with RCC1. These results identify two activities sufficient to mimic chromatin-mediated spindle assembly, and establish a foundation for future experiments to reconstitute spindle assembly entirely from purified components.

Loss to Follow up in Patients with Proliferative Diabetic Retinopathy Treated with Anti-VEGF Therapy and/or Panretinal Photocoagulation in the United States.

PURPOSE: To determine the rate of loss to follow up (LTFU) in patients with proliferative diabetic retinopathy (PDR) treated with anti-VEGF therapy and/or panretinal photocoagulation (PRP) in the United States. DESIGN: Retrospective cohort study using the national IRIS® (Intelligent Research in Sight) Registry data. SUBJECTS: A total of 73 595 eyes of 56 590 patients with PDR diagnosed between 2013 and 2015 and treated between 2013 and 2018. METHODS: Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Loss to follow up was no follow up within 12 months from last treatment. RESULTS: For patient eyes treated for PDR, 11.7% (95% CI, 11.5-12.0) were LTFU. Among patients with PDR treated with anti-VEGF therapy alone, PRP alone, and anti-VEGF and PRP, the rates of LTFU were 12.3% (95% CI, 11.8-12.7), 12.6% (95% CI, 12.1-13.0), and 10.8% (95% CI, 10.4-11.1), respectively. Risk factors for LTFU include Black or African American race/ethnicity (odds ratio [OR], 1.26; 95% CI, 1.13-1.41; P < 0.001), Hispanic ethnicity (OR, 1.28; 95% CI, 1.16-1.42; P < 0.001), Native American/Alaska Native or Native Hawaiian/Other Pacific Islander race/ethnicity (OR, 2.69; 95% CI, 2.14-3.38; P < 0.001), and unilateral disease (OR, 2.05; CI, 1.88-2.23; P < 0.001). Odds for LTFU were higher with patients with baseline vision of 20/50 to 20/200 (OR, 1.25; 95% CI, 1.15-1.36; P < 0.001) and with vision worse than 20/200 (OR, 1.22; 95% CI, 1.05-1.42; P = 0.01) than for patient eyes with a baseline visual acuity of 20/40 or better. Odds for LTFU were lower for Medicare Fee-for-Service (OR, 0.71; 95% CI, 0.64-0.79; P < 0.001) and Medicare Managed (OR, 0.66; 95% CI, 0.56-0.78; P < 0.001) compared with private insurance. Odds for LTFU were lower for patients treated in the Midwest (OR, 0.72; 95% CI, 0.64-0.81; P < 0.001) and West (OR, 0.83; 95% CI, 0.74-0.94; P = 0.003) compared with in the South region. CONCLUSIONS: The rate of LTFU is between 10% and 12% among patients with PDR who were treated with anti-VEGF injections and/or PRP. Risk factors include Black or African American race/ethnicity, Hispanic ethnicity, baseline vision worse than 20/40, private insurance, South region, and unilateral disease. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health.

The human retina is a multilayered tissue that offers a unique window into systemic health. Optical coherence tomography (OCT) is widely used in eye care and allows the noninvasive, rapid capture of retinal anatomy in exquisite detail. We conducted genotypic and phenotypic analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed OCT layer cross-phenotype association analyses (OCT-XWAS), associating retinal thicknesses with 1866 incident conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association studies (GWASs), identifying inherited genetic markers that influence retinal layer thicknesses and replicated our associations among the LIFE-Adult Study (N = 6313). Last, we performed a comparative analysis of phenome- and genome-wide associations to identify putative causal links between retinal layer thicknesses and both ocular and systemic conditions. Independent associations with incident mortality were detected for thinner photoreceptor segments (PSs) and, separately, ganglion cell complex layers. Phenotypic associations were detected between thinner retinal layers and ocular, neuropsychiatric, cardiometabolic, and pulmonary conditions. A GWAS of retinal layer thicknesses yielded 259 unique loci. Consistency between epidemiologic and genetic associations suggested links between a thinner retinal nerve fiber layer with glaucoma, thinner PS with age-related macular degeneration, and poor cardiometabolic and pulmonary function with a thinner PS. In conclusion, we identified multiple inherited genetic loci and acquired systemic cardio-metabolic-pulmonary conditions associated with thinner retinal layers and identify retinal layers wherein thinning is predictive of future ocular and systemic conditions.