Cardiovascular risk in anti-VEGF treatment of neovascular age-related macular degeneration.

OBJECTIVE: Assess 5-year all-cause mortality (ACM), hemorrhagic stroke, ischemic stroke, and myocardial infarction (MI) risks in nAMD patients receiving anti-VEGF injections compared with controls. DESIGN: Population-based retrospective cohort study using a U.S. federated health research network, containing de-identified data of 96 million patients from 1/1/2003 to 3/6/2023. PARTICIPANTS: nAMD Patients with anti-VEGF injections. Controls included nAMD patients without anti-VEGF injections, non-exudative AMD patients, and patients without AMD. METHODS: Patients were identified using nAMD ICD-10 and anti-VEGF CPT codes and matched for age, sex, and comorbidities. Five-year relative risk of ACM (RR1), hemorrhagic stroke (RR2), ischemic stroke (RR3), and MI (RR4) in nAMD patients receiving anti-VEGF injections were calculated. RESULTS: A total of 27,609 nAMD patients (mean diagnosis age [SD], [78.2 (10.3)]) received anti-VEGF injections; 769 nAMD patients without injections (75.8 [12.2]), 27,599 non-exudative AMD patients (78.2 [10.3]), and 21,902 no-AMD patients (76.1 [10.5]) were identified. After matching, nAMD patients receiving injections did not show increased risk versus nAMD patients without injections (RR1, 0.66; 95% CI [0.53, 0.82]), (RR2, 1.00 [0.42, 2.38]), (RR3, 1.70 [0.92,3.13]), (RR4, 0.63 [0.33, 1.18]). No increased risk was found compared to non-exudative AMD patients (RR1, 0.99 [0.95, 1.03]), (RR2, 0.94 [0.83,1.07]), (RR3, 1.04 [0.96, 1.12]), (RR4, 0.99 [0.91, 1.08]). Increased risk for ACM was observed versus no-AMD patients (RR1, 1.21 [1.15, 1.27]), but no other differences were found (RR2, 0.81 [0.70, 0.93]), (RR3, 1.00 [0.92, 1.09]), (RR4, 0.986 [0.90, 1.09]). CONCLUSION: Anti-VEGF injections were not associated with major cardiovascular events in nAMD patients over 5 years.

Melatonin and Risk of Age-Related Macular Degeneration.

Importance: Melatonin has been shown to oppose several processes that are known to mediate age-related macular degeneration (AMD), but whether melatonin can confer benefits against AMD remains unclear. Objective: To examine the association between melatonin supplementation and the risk of the development or progression of AMD. Design, Setting, and Participants: This retrospective cohort study accessed data from TriNetX, a national database of deidentified electronic medical records from both inpatient and outpatient health care organizations across the US, between December 4, 2023, and March 19, 2024. Patients aged 50 years or older, 60 years or older, and 70 years or older with no history of AMD (AMD-naive group) and with a history of nonexudative AMD (nonexudative AMD group) were queried for instances of melatonin medication codes between November 14, 2008, and November 14, 2023. Patients were then classified into either a melatonin group or a control group based on the presence of medication codes for melatonin. Propensity score matching (PSM) was performed to match the cohorts based on demographic variables, comorbidities, and nonmelatonin hypnotic medication use. Exposure: The presence of at least 4 instances of melatonin records that each occurred at least 3 months apart. Main Outcomes and Measures: After PSM, the melatonin and the control cohorts were compared to evaluate the risk ratios (RRs) and the 95% CIs of having an outcome. For the AMD-naive group, the outcome was defined as a new diagnosis of any AMD, whereas for the nonexudative AMD group, the outcome was progression to exudative AMD. Results: Among 121 523 patients in the melatonin-naive group aged 50 years or older (4848 in the melatonin cohort [4580 after PSM; mean (SD) age, 68.24 (11.47) years; 2588 female (56.5%)] and 116 675 in the control cohort [4580 after PSM; mean (SD) age, 68.17 (10.63) years; 2681 female (58.5%)]), melatonin use was associated with a reduced risk of developing AMD (RR, 0.42; 95% CI, 0.28-0.62). Among 66 253 patients aged 50 years or older in the nonexudative AMD group (4350 in the melatonin cohort [4064 after PSM; mean (SD) age, 80.21 (8.78) years; 2482 female (61.1%)] and 61 903 in the control cohort [4064 patients after PSM; mean (SD) age, 80.31 (8.03) years; 2531 female (62.3%)]), melatonin was associated with a reduced risk of AMD progression to exudative AMD (RR, 0.44; 95% CI, 0.34-0.56). The results were consistent among subsets of individuals aged 60 years or older (AMD-naive cohort: RR, 0.36 [95% CI, 0.25-0.54]; nonexudative AMD cohort: RR, 0.38 [95% CI, 0.30-0.49]) and 70 years or older (AMD-naive cohort: RR, 0.35 [95% CI, 0.23-0.53]; nonexudative AMD cohort: RR, 0.40 [95% CI, 0.31-0.51]). Conclusions and Relevance: Melatonin use was associated with a decreased risk of development and progression of AMD. Although lifestyle factors may have influenced this association, these findings provide a rationale for further research on the efficacy of using melatonin as a preventive therapy against AMD.

Longitudinal Trends and Disparities in Diabetic Retinopathy Within an Aggregate Health Care Network.

Importance: Diabetic retinopathy (DR) is a leading cause of blindness in the US, warranting updates on its prevalence and incidence in the setting of advancements in diabetic care over recent years. Objective: To determine recent trends in DR prevalence stratified by baseline demographics to identify those populations at greater risk. Design, Setting, and Participants: This was a cross-sectional epidemiologic evaluation conducted using deidentified data from the large federated TriNetX Analytics health research network composed of 56 health care organizations in the US. Patients from 2015 to 2022 who had an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code of type 1 DR (T1DR) or type 2 DR (T2DR) were included in this analysis. Patients were further stratified by age cohorts (20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years, and 70 years or older), race and ethnicity, and sex. Main Outcomes and Measures: Prevalence per 100 000 patients and prevalence odds ratios (ORs) were calculated in Microsoft Excel and Posit (formerly RStudio). Results: A total of 359 126 patients with T1DR or T2DR (mean [SD] age, 67 [14] years; 52% female) were included in this study between January 1, 2015, and December 21, 2022. T1DR increased in prevalence from 2015 to 2022, with T1DR increasing 1.15-fold affecting 70.4 patients per 100 000 in 2022. T2DR increased 1.07-fold affecting 461.7 patients per 100 000 in 2022. For T1DR, the cohort aged 20 to 39 years had the most substantial increase at 4.7 and 1.96 fold. Overall, White males had the largest prevalence ORs of T1DR at 1.41 (95% CI, 1.36-1.47) compared with White females (reference group). In T2DR, patients aged 20 to 39 years again had a 2.5- and 1.6-fold prevalence increase from 2015 to 2022. Regardless of age group, Hispanic males demonstrated larger prevalence OR at 4.08 (95% CI, 3.97-4.19) compared with White females followed by Hispanic females at 2.49 (95% CI, 2.42-2.56), Black males at 2.23 (95% CI, 2.17-2.29), and Black females at 2.00 (95% CI, 1.95-2.05). Conclusion and Relevance: The prevalence of both T1DR and T2DR increased in this network from 2015 to 2022, with individuals aged 20 to 39 years showing large increases. Additionally, T2DR was associated with greater increases in both Hispanic and Black communities. These findings support DR screening in young adults and for T2DR interventions specifically designed for racial and ethnic minoritized patients most affected by disease. Future investigations are warranted to further investigate these trends among young adults.

The Risk of Optic Neuritis following mRNA Coronavirus Disease 2019 Vaccination Compared to Coronavirus Disease 2019 Infection and Other Vaccinations.

PURPOSE: To determine the risk of optic neuritis (ON) after mRNA Coronavirus Disease 2019 (COVID-19) vaccine administration. DESIGN: U.S. National aggregate database retrospective cohort study. PARTICIPANTS: Patients were placed into cohorts based on mRNA COVID-19 vaccination status (no vaccine and positive history of COVID-19 infection, 1 vaccine, or 2 vaccines received) from December 2020 to June 2022. Two control cohorts were created with patients vaccinated against influenza or tetanus diphtheria and pertussis (Tdap) from June 2018 to December 2019. Patients with any history of ON or significant risk factors for ON development including infectious, inflammatory, and neoplastic diseases were excluded. METHODS: A large deidentified database was queried for the Common Procedural Technology codes for immunization encounters specific to first dose and second dose of mRNA COVID-19 vaccine, influenza, or Tdap. Cohorts were 1:1 propensity score matched on age, sex, race, and ethnicity. The risk of ON development after vaccination was calculated and compared for all 5 cohorts with 95% confidence intervals (CIs) reported. MAIN OUTCOME MEASURES: Risk ratio (RR) of ON 21 days after vaccination (or COVID-19 infection) and incidence of ON per 100 000 individuals. RESULTS: After matching, the first dose COVID-19 and influenza vaccine cohorts (n = 1 678 598, mean age [standard deviation] at vaccination of 45.5 [23.3] years and 43.2 [25.5] years, 55% female) the RR of developing ON was 0.44 (95% CI, 0.28-0.80). The first dose of COVID-19 and Tdap vaccinations (n = 797 538, mean age 38.9 [20.0] years, 54.2% female) cohort had 10 and 16 patients develop ON (RR, 0.63; 95% CI, 0.28-1.38). Comparison of COVID-19-vaccinated patients (n = 3 698 848, 48.2 [21.5] years, 54.7% female) to unvaccinated and COVID-19-infected patients (n = 3 698 848, 49.6 [22.0] years, 55.2% female) showed 49 and 506 patients developing ON, respectively (RR, 0.09; 95% CI, 0.07-0.12). The incidence per 100 000 for ON was 1 in the first dose COVID-19 vaccine cohort, 2 in the influenza cohort, and 2 in the Tdap cohort, and 14 in the COVID-19-infected and unvaccinated cohorts. CONCLUSIONS: Risk of ON after mRNA COVID-19 vaccination is rare and comparable to Tdap vaccination, decreased compared with influenza vaccination, and decreased compared with COVID-19 infection in the absence of vaccination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Changes in Prevalence of Idiopathic Intracranial Hypertension in the United States Between 2015 and 2022, Stratified by Sex, Race, and Ethnicity.

BACKGROUND AND OBJECTIVES: With the obesity epidemic within the United States, the prevalence of idiopathic intracranial hypertension (IIH) is predicted to rise. IIH prevalence and racial disparities have rarely been reported in the United States. The purpose of this study was to evaluate the prevalence of IIH in a large national database while stratifying by sex, age, race, and ethnicity. METHODS: This was a cross-sectional epidemiologic evaluation conducted in the TriNetX US Collaborative network using data from 2015 to 2022. Patients with an International Classification of Diseases code of IIH and papilledema or unspecified papilledema were included in the study. Any secondary cause of intracranial hypertension including cerebral neoplasms and hydrocephalus were excluded from the study. IIH trends were later compared with TriNetX cohort obesity trends. Prevalence and prevalence odds ratios (ORs) were calculated in Microsoft Excel and R Studio. RESULTS: Among 85 million patients in this database, a 1.35 times increase in the prevalence of IIH occurred between 2015 and 2022 from 7.3 (95% CI 6.9-7.7) individuals per 100,000 to 9.9 (95% CI 9.5-10.3) individuals per 100,000 in 2022. In 2022, Black female individuals had the highest prevalence of IIH with 22.7 individuals per 100,000 compared with the 13.7 White female individuals per 100,000. Patients aged 11-17 years showed the largest growth of IIH prevalence with female individuals increasing by 10 individuals per 100,000 by 2022. Overall, Black and Hispanic patients had the largest prevalence OR of IIH at 1.66 (95% CI 1.49-1.85) and 1.33 (95% CI 1.14-1.56), respectively, compared with White female patients. DISCUSSION: IIH is a rapidly increasing health care concern for the US population, particularly among adolescent patients. Black and Hispanic female individuals are most predominately affected by this incapacitating disorder.

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort.

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. RESULTS: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. CONCLUSION: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:626-633.].

The Incidence, Time to Development, and Risk Factors for Fellow Eye Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: Little is known about factors affecting risk or time to development of fellow eye retinal vein occlusion (RVO). The purpose of this study was to examine the incidence and risk factors for fellow eye RVO. PATIENTS AND METHODS: This was a retrospective case-control study comparing unilateral and fellow eye RVO patients. This study was exempt by the Cleveland Clinic Institutional Review Board. RESULTS: Out of 1,083 patients, fellow eye RVO had a cumulative incidence of 3.6% (95% CI 2.61, 4.94) with a median time to development of 18 months (95% CI 6.0, 28.0). Fellow eye disease was associated with multiple characteristics including chronic kidney disease (odds ratio [OR] 3.78, 95% CI 1.89 to 7.55) and diabetic retinopathy (3.18, 1.57 to 6.44). CONCLUSION: While fellow eye RVO is relatively rare, it typically occurs within the first few years following initial diagnosis. Multiple characteristics were associated with fellow eye disease and time to onset. [Ophthalmic Surg Lasers Imaging Retina 2023;54:471-476.].

Increased medical student understanding of dementia through virtual embodiment.

Given the growing prevalence of Alzheimer's disease (AD), we assessed the impact of virtually embodying someone with progressive AD. This pilot explored students' understanding of individuals' needs with dementia, as well as, the efficacy of virtual reality (VR) as a curricular tool. Second-year medical students (n = 150) completed a pre-survey, Embodied Labs, Inc. Beatriz Lab VR module, and a post-survey. Most students knew someone with dementia (72%), were a family member of someone with dementia (52%) or had worked with a patient (61%) with dementia. Using paired survey questions, students reported significant increases in understanding how their lives would be affected by dementia (71% vs. 94%) and the needs of a person with dementia (64% vs. 95%) after VR. They reported increased understanding of being a caregiver of someone with dementia (24% vs. 81%) and the impact it can have on the entire family (64% vs. 97%). Overall students agreed this simulation made them think about their approach to clinical skills (94%) and should be utilized more in the curriculum (76%). This pilot study indicated that this VR experience can be used to advance understanding of a person's experiences with dementia and that integrating VR into the medical curricula should be considered.

Educational Case: Giant Cell Tumor of the Bone in Both the Axial and Appendicular Skeleton.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Acute presentation of idiopathic intracranial hypertension with severe vision deficits.

Fulminant idiopathic intracranial hypertension is a rare presentation of idiopathic intracranial hypertension in which visual decline occurs within 4 weeks of initial symptom presentation. Idiopathic intracranial hypertension usually presents with headaches, visual disturbances, and in women who are overweight. We present a case of idiopathic intracranial hypertension in which a female patient presented with rapid, severe vision loss within 8 days of symptom presentation and no other idiopathic intracranial hypertension symptoms. This case highlights a rare presentation of Fulminant idiopathic intracranial hypertension and the need for a quick diagnosis and treatment to preserve vision.