Retinal Ischemic Perivascular Lesions in Individuals With Atrial Fibrillation.

Background We previously demonstrated that retinal ischemic perivascular lesions (RIPLs), which are indicative of ischemia in the middle retina, may be a biomarker of ischemic cardiovascular disease. In this study, we sought to determine the relationship between RIPLs and atrial fibrillation, a common source of cardiac emboli. Methods and Results In this case-control study, we identified individuals between the ages of 50 and 90 years who had undergone macular spectral domain optical coherence tomography imaging. Individuals with atrial fibrillation were identified, and age- and sex-matched individuals from the same pool, but without a diagnosis of atrial fibrillation, were selected as controls. Spectral domain optical coherence tomography scans were reviewed by 3 independent and masked observers for presence of RIPLs. The relationship between RIPLs and atrial fibrillation was analyzed using multivariable logistic regression models. There were 106 and 91 subjects with and without atrial fibrillation, respectively. The percentage of subjects with RIPLs was higher in the atrial fibrillation group compared with the control group (57.5% versus 37.4%; P=0.005). After adjusting for age, sex, smoking history, hypertension, diabetes, coronary artery disease, carotid stenosis, stroke, and myocardial infarction, the presence of RIPLs was significantly associated with atrial fibrillation, with an odds ratio of 1.91 (95% CI, 1.01-3.59). Conclusions RIPLs are significantly associated with atrial fibrillation, independent of underlying ischemic heart disease or cardiovascular risk factors. This association may inform the diagnostic cardiovascular workup for individuals with RIPLs incidentally detected on optical coherence tomography scan of the macula.

Correction: Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

[This corrects the article DOI: 10.1371/journal.pone.0269231.].

Validation of the Prognostic Usefulness of the Gene Expression Profiling Test in Patients with Uveal Melanoma.

PURPOSE: To validate the prognostic usefulness of gene expression profile (GEP) testing in patients with uveal melanoma. To determine whether combining tumor size with the GEP classification provides additional prognostic value. DESIGN: Retrospective analysis. PARTICIPANTS: Patients with a diagnosis of choroidal melanoma examined at Yale New Haven Hospital; University of California, San Diego; and Memorial Sloan Kettering Cancer Center. METHODS: Patients' demographic and clinical data and tumor characteristics were collected. Univariate and multivariate Cox hazard regression analysis were used to assess the association between tumor characteristics and GEP classification with metastasis as an outcome. MAIN OUTCOME MEASURES: Metastasis-free survival (MFS). RESULTS: Of the 337 individuals included in the study, 87 demonstrated metastases. The mean follow-up time was 37.2 (standard deviation [SD], 40.2) months for patients with metastases and 55.0 (SD, 49.3) months for those without metastases. Tumors of larger thickness and GEP class 2 (vs. class 1) were associated significantly with increased risk of metastasis. Tumor thickness showed better prognostic usefulness than GEP classification (Wald statistic, 40.7 and 24.2, respectively). Class 2 tumors with a thickness of 7.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 7.0 mm (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.61-6.51), whereas class 1 tumors with a thickness of 9.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 9.0 mm (HR, 2.07; 95% CI, 0.86-4.99). No difference in MFS was found between patients with class 1A tumors compared with those with class 1B tumors (P = 0.8). Patients with class 2 tumors showed an observed 5-year MFS of 47.5% (95% CI, 36.0%-62.8%). CONCLUSIONS: Tumor size was the most significant predictor of metastasis and provided additional prognostic value independent of GEP classification. In addition, rates of metastasis for class 2 tumors were lower than estimates reported by Castle Bioscience, and no difference in rates of metastasis were found between class 1A and 1B tumors. This indicates that tumor size should be accounted for when relying on GEP for prognostication and that patients with GEP class 1A or 1B tumors may benefit from the same metastatic surveillance protocols. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Social Determinants of Health Data Availability for Patients with Eye Conditions.

Purpose: To quantify and characterize social determinants of health (SDoH) data coverage using single-center electronic health records (EHRs) and the National Institutes of Health All of Us research program. Design: Retrospective cohort study from June 2014 through June 2021. Participants: Adults 18 years of age or older with a diagnosis of diabetic retinopathy, glaucoma, cataracts, or age-related macular degeneration. Methods: For All of Us, research participants completed online survey forms as part of a nationwide prospective cohort study. In local EHRs, patients were selected based on diagnosis codes. Main Outcome Measures: Social determinants of health data coverage, characterized by the proportion of each disease cohort with available data regarding demographics and socioeconomic factors. Results: In All of Us, we identified 23 806 unique adult patients, of whom 2246 had a diagnosis of diabetic retinopathy, 13 448 had a diagnosis of glaucoma, 6634 had a diagnosis of cataracts, and 1478 had a diagnosis of age-related macular degeneration. Survey completion rates were high (99.5%-100%) across all cohorts for demographic information, overall health, income, education, and lifestyle. However, health care access (12.7%-29.4%), housing (0.7%-1.1%), social isolation (0.2%-0.3%), and food security (0-0.1%) showed significantly lower response rates. In local EHRs, we identified 80 548 adult patients, of whom 6616 had a diagnosis of diabetic retinopathy, 26 793 had a diagnosis of glaucoma, 40 427 had a diagnosis of cataracts, and 6712 had a diagnosis of age-related macular degeneration. High data coverage was found across all cohorts for variables related to tobacco use (82.84%-89.07%), alcohol use (77.45%-83.66%), and intravenous drug use (84.76%-93.14%). However, low data coverage (< 50% completion) was found for all other variables, including education, finances, social isolation, stress, physical activity, food insecurity, and transportation. We used chi-square testing to assess whether the data coverage varied across different disease cohorts and found that all fields varied significantly (P < 0.001). Conclusions: The limited and highly variable data coverage in both local EHRs and All of Us highlights the need for researchers and providers to develop SDoH data collection strategies and to assemble complete datasets.

Novel Association between Opioid Use and Increased Risk of Retinal Vein Occlusion Using the National Institutes of Health All of Us Research Program.

Purpose: To assess for risk factors for retinal vein occlusion (RVO) among participants in the National Institutes of Health All of Us database, particularly social risk factors that have not been well studied, including substance use. Design: Retrospective, case-control study. Participants: Data were extracted for 380 adult participants with branch retinal vein occlusion (BRVO), 311 adult participants with central retinal vein occlusion (CRVO), and 1520 controls sampled among 311 640 adult participants in the All of Us database. Methods: Data were extracted regarding demographics, comorbidities, income, housing, insurance, and substance use. Opioid use was defined by relevant diagnosis and prescription codes, with prescription use > 30 days. Controls were sampled at a 4:1 control to case ratio from a pool of individuals aged > 18 years without a diagnosis of RVO and proportionally matched to the demographic distribution of the 2019 U.S. census. Multivariable logistic regression identified medical and social determinants significantly associated with BRVO or CRVO. Statistical significance was defined as P < 0.05. Main Outcome Measure: Development of BRVO or CRVO based on diagnosis codes. Results: Among patients with BRVO, the mean (standard deviation) age was 70.1 (10.5) years. The majority (53.7%) were female. Cases were diverse; 23.7% identified as Black, and 18.4% identified as Hispanic or Latino. Medical risk factors including glaucoma (odds ratio [OR], 3.29; 95% confidence interval [CI], 2.22-4.90; P < 0.001), hypertension (OR, 2.15; 95% CI, 1.49-3.11; P < 0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.38; P = 0.004) were re-demonstrated to be associated with BRVO. Black race (OR, 2.64; 95% CI, 1.22-6.05; P = 0.017) was found to be associated with increased risk of BRVO. Past marijuana use (OR, 0.68; 95% CI, 0.50-0.92; P = 0.013) was associated with decreased risk of BRVO; however, opioid use (OR, 1.98; 95% CI, 1.41-2.78; P < 0.001) was associated with a significantly increased risk of BRVO. Similar associations were found for CRVO. Conclusions: Understanding RVO risk factors is important for primary prevention and improvement in visual outcomes. This study capitalizes on the diversity and scale of a novel nationwide database to elucidate a previously uncharacterized association between RVO and opioid use.

Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

PURPOSE: Inadequacies in healthcare access and utilization substantially impact outcomes for diabetic patients. The All of Us database offers extensive survey data pertaining to social determinants that is not routinely available in electronic health records. This study assesses whether social determinants were associated with an increased risk of developing proliferative diabetic retinopathy or related complications (e.g. related diagnoses or procedures). METHODS: We identified 729 adult participants in the National Institutes of Health All of Us Research Program data repository with diabetic retinopathy (DR) who answered survey questions pertaining to healthcare access and utilization. Electronic health record data regarding co-morbidities, laboratory values, and procedures were extracted. Multivariable logistic regression with bi-directional stepwise variable selection was performed from a wide range of predictors. Statistical significance was defined as p<0.05. RESULTS: The mean (standard deviation) age of our cohort was 64.9 (11.4) years. 15.2% identified as Hispanic or Latino, 20.4% identified as Black, 60.6% identified as White, and 19.3% identified as Other. 10-20% of patients endorsed several reasons for avoiding or delaying care, including financial concerns and lack of access to transportation. Additional significant social determinants included race and religion discordance between healthcare provider and patient (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.41, p = 0.03) and caregiver responsibilities toward others (OR 3.14, 95% CI 1.01-9.50, p = 0.04). CONCLUSIONS: Nationwide data demonstrate substantial barriers to healthcare access among DR patients. In addition to financial and social determinants, race and religion discordance between providers and patients may increase the likelihood of PDR and related complications.

Polymorphous low-grade adenocarcinoma with cavernous sinus involvement presenting as third nerve palsy.

Purpose: Polymorphous low-grade adenocarcinoma is a tumor of the salivary glands that typically localizes within the oral cavity. We present a case of isolated third cranial nerve palsy as the initial presentation of polymorphous low-grade adenocarcinoma involving the left cavernous sinus in a patient status post glaucoma surgery. Observations: A 68-year-old woman status post glaucoma drainage device implantation in her left eye presented with an isolated left third nerve palsy ten weeks postoperatively. Differential diagnoses included microvascular ischemic neuropathy, postoperative ptosis, and compressive mass. MRI revealed a left cavernous sinus mass, and subsequent excisional biopsy revealed a diagnosis of polymorphous low-grade adenocarcinoma. Conclusions: There are few cases reporting polymorphous low-grade adenocarcinoma originating from and extending beyond the nasopharynx. This report emphasizes an unexpected neuro-ophthalmic manifestation of this salivary gland tumor.

Social determinants associated with loss of an eye in the United States using the All of Us nationwide database.

PURPOSE: To identify common factors associated with the loss of an eye using the NIH All of Us database. METHODS: In this case-controlled study, we extracted electronic health record and socio-demographic data for 231 cases of eye loss from All of Us enrollment sites. Controls (N = 924) matched the demographic characteristics of the 2020 United States Census. Bivariate analyses and multivariable logistic regression identified variables significantly associated with increased odds of eye loss. OUTCOME MEASURES: Medical and social determinants associated with increased odds of losing an eye. RESULTS: Among cases, the average age (standard deviation) was 60.1 (14.4) years. The majority (125, 54.1%) were male. 87 (37.7%) identified as African American, and 49 (21.2%) identified as Hispanic or Latino. Loss of eye was more likely in those with ocular tumor (odds ratio [OR] 421.73, 25 95% confidence interval [CI] 129.81-1959.80, p < .001), trauma (OR 13.38, 95% CI 6.64-27.43, p < .001), infection (OR 11.46, 95% CI 4.11-32.26, p = .001) or glaucoma (OR 8.33, 95% CI 4.43- 15.81, p < .001). African American (OR 2.39, 95% CI 1.39-4.09, p = .002) and Hispanic or Latino (OR 1.80, 95% CI 1.01-3.15, p = .04) participants were disproportionately affected. CONCLUSIONS: Racial and ethnic disparities exist among those with loss of an eye from underlying conditions. Addressing health inequities may mitigate the risk of this morbid outcome.

Prevalence of subclinical retinal ischemia in patients with cardiovascular disease - a hypothesis driven study.

BACKGROUND: Cardiovascular disease is the leading cause of mortality and disability worldwide. A noninvasive test that can detect underlying cardiovascular disease has the potential to identify patients at risk prior to the occurrence of adverse cardiovascular events. We sought to determine whether an easily observed imaging finding indicative of retinal ischemia, which we term 'retinal ischemic perivascular lesions' (RIPLs), could serve as a biomarker for cardiovascular disease. METHODS: We reviewed optical coherence tomography (OCT) scans of individuals, with no underlying retinal pathology, obtained at UC San Diego Health from July 2014 to July 2019. We identified 84 patients with documented cardiovascular disease and 76 healthy controls. OCT scans were assessed for evidence of RIPLs. In addition, the 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculator was used to risk-stratify the subjects into four different categories. FINDINGS: Patients with documented cardiovascular disease had higher number of RIPLs compared to healthy controls (2.8 vs 0.8, p < 0.001). After adjusting for age, sex, smoking history, systolic blood pressure and triglycerides, cholesterol and hemoglobin A1C levels, each RIPL was associated with an odds ratio of having cardiovascular disease of 1·60 (1.09-2>37). The number of RIPLs in individuals with intermediate and high 10-year ASCVD risk scores was higher than in those with low ASCVD risk scores (1.7 vs 0.64, p = 0.02 and 2.9 vs 0.64, p 0.002, respectively). INTERPRETATION: The presence of RIPLs, which are anatomical markers of prior retinal ischemic infarcts, is suggestive of coexisting cardiovascular disease. RIPLs detection, obtained from routine retinal scans, may thus provide an additional biomarker to identify patients at risk of developing adverse cardiovascular events. FUNDING: None.

Relationship between Retinal Vascular Occlusions and Cognitive Dementia in a Large Cross-Sectional Cohort.

PURPOSE: To examine the association between cognitive dementia and retinal vascular occlusions. DESIGN: A retrospective, cross-sectional study. METHODS: Single-institution study population: we reviewed the electronic medical records of 37,208 individuals older than 65 years of age who were evaluated by an ophthalmologist or an optometrist and who also had a medical visit to our institution over a 6-year period. Individuals with and without retinal vascular occlusions were identified by International Classification of Diseases, version 10 (ICD-10) diagnostic codes. MAIN OUTCOME: we analyzed the association between dementia and retinal vascular occlusions after adjusting for covariates which included age, sex, stroke, diabetes mellitus, and hypertension using multiple logistic regression analyses. RESULTS: Compared to subjects without retinal vascular occlusions, those with retinal vascular occlusions had a higher prevalence of dementia (6.7% vs. 9.3%, respectively; P < .001). After adjusting for either age or stroke, there were no significant associations between retinal vascular occlusions and dementia. CONCLUSIONS: Individuals with retinal vascular occlusions have a higher prevalence of dementia. However, this association is secondary to shared underlying risk factors in this population, such as older age and stroke.

Artificial Intelligence for Automated Overlay of Fundus Camera and Scanning Laser Ophthalmoscope Images.

Purpose: The purpose of this study was to evaluate the ability to align two types of retinal images taken on different platforms; color fundus (CF) photographs and infrared scanning laser ophthalmoscope (IR SLO) images using mathematical warping and artificial intelligence (AI). Methods: We collected 109 matched pairs of CF and IR SLO images. An AI algorithm utilizing two separate networks was developed. A style transfer network (STN) was used to segment vessel structures. A registration network was used to align the segmented images to each. Neither network used a ground truth dataset. A conventional image warping algorithm was used as a control. Software displayed image pairs as a 5 × 5 checkerboard grid composed of alternating subimages. This technique permitted vessel alignment determination by human observers and 5 masked graders evaluated alignment by the AI and conventional warping in 25 fields for each image. Results: Our new AI method was superior to conventional warping at generating vessel alignment as judged by masked human graders (P < 0.0001). The average number of good/excellent matches increased from 90.5% to 94.4% with AI method. Conclusions: AI permitted a more accurate overlay of CF and IR SLO images than conventional mathematical warping. This is a first step toward developing an AI that could allow overlay of all types of fundus images by utilizing vascular landmarks. Translational Relevance: The ability to align and overlay imaging data from multiple instruments and manufacturers will permit better analysis of this complex data helping understand disease and predict treatment.

Pseudophakic glaucoma and angle closure in a patient with an anterior chamber intraocular lens.

PURPOSE: To report use of ultrasound biomicroscopy (UBM) and anterior segment ocular coherence tomography (AS-OCT) in a case of pseudophakic glaucoma in a patient with an anterior chamber intraocular lens. OBSERVATIONS: UBM and AS-OCT were critical in determining a non-drug related etiology of angle closure. Images indicated anterior obstruction of the pupil secondary to anterior chamber intraocular lens, but also posterior obstruction of the pupil secondary to the anterior hyaloid face. CONCLUSIONS: When evaluating a patient with suspected angle closure, it is important to perform a full ophthalmologic examination, including gonioscopy, as well as a thorough review of past medical history and medications so as not to miss systemic-related etiologies. Imaging with B-scan, UBM, and, more recently in the last decade, AS-OCT is a key component of evaluation of a patient in angle closure, especially one with a complex medical and ocular history.