Impact of iris color on uveal melanoma-related outcomes in 7245 patients at a single ocular oncology center.

PURPOSE: To determine the relationship between iris color and uveal melanoma (UM)-related metastasis and death in a large cohort of patients from a single ocular oncology center. DESIGN: Retrospective case series. SUBJECTS: Patients diagnosed with UM between February 1971 and August 2007. METHODS: Patient information was obtained from chart documentation. MAIN OUTCOME MEASURES: UM-related metastasis and death. RESULTS: Out of 7245 patients, iris color was blue in 3702 (51%), green in 1458 (20%), and brown in 2085 (29%). Mean age was 58 ± 15 years and mean tumor thickness was 5.5 ± 3.3 millimeters. Some clinical features differed between iris color groups, with the blue irides group having a larger proportion of post-equatorial tumors with significantly closer proximity to the foveola and optic disc compared to the brown irides group. At a mean follow-up of 75 months, there was no statistically significant difference in metastasis between the various iris color groups. On univariate analysis, those with blue irides showed a higher incidence of UM-related death compared to the green and brown irides groups (8.3%, 5.9% and 7.5% respectively, p value = 0.02). Kaplan-Meier event free survival from UM-related death significantly differed only between the blue and green irides groups (p value = 0.007) with the green irides group showing the highest survival. However, on multivariate analysis, iris color was not predictive of UM-related death. CONCLUSION: Iris color was not predictive of UM-related metastasis or death. However, Kaplan-Meier survival at 20 years was poorest for blue irides group compared to green.

Ophthalmology procedure trends in the United States during the COVID-19 pandemic.

PURPOSE: To evaluate the relationship between the COVID-19 pandemic and ophthalmic procedural volume. METHODS: A retrospective cohort study using TriNetX, a federated electronic health record's research network was done. Monthly Current Procedural Terminology-specific volumes per healthcare organization were clustered chronologically to calculate average volumes into 3-month seasons to calculate average procedural volumes. An aggregate of the total pandemic period (March 2020-August 2021) was compared to corresponding figures in pre-pandemic timeframes. RESULTS: Intravitreal injections were the most prevalent procedure in this time period with 320,106 occurrences. Phacoemulsification cataract surgery was the second most prevalent (N = 176,095) procedure. From March 2020 to August 2021, a mean pandemic volume of 266.7 (SD = 15) was observed, a 5% decrease (p < 0.05) in procedures compared to the pre-pandemic mean of 280.8 (SD = 26.1). Spring 2020 exhibited the sharpest seasonal decrease in procedural volume (- 88%). The largest count of statistically significant increases in procedure volume was in Spring 2021 (+ 18%). The aggregate mean volume per HCO showed significant decreases for 11 out of 17 procedures in the 12 month March 2020-February 2021 timeframe and significant decreases for 10 out of 17 procedures over the 18-month March 2020-August 2021 pandemic period. CONCLUSIONS: This study highlights the relative inverse relationship between COVID-19 cases and ophthalmic procedure volume in America. Quantifying ophthalmic procedure trends is important in retrospectively assessing surgical disruptions and prospectively accommodating delayed surgeries. Furthermore, awareness of these trends could help ophthalmologists prepare should similar disruptions occur in the setting of future pandemics or national disasters.

Cavitary Retinoblastoma Imaged on Magnetic Resonance Imaging.

Cavitary retinoblastoma is a rare subtype, characterized by the presence of translucent cavities within the solid malignancy. A 2-year-old boy with bilateral retinoblastoma was found to have a unique cavitary retinoblastoma with seven cavities, more than previously reported, and large enough to be imaged on magnetic resonance imaging. [J Pediatric Ophthalmol Strabismus. 2023;60(1):e1-e4.].

Relationship between Fitzpatrick Skin Type and The Cancer Genome Atlas Classification with Melanoma-Related Metastasis and Death in 854 Patients at a Single Ocular Oncology Center.

BACKGROUND: The Fitzpatrick Skin Type (FST) is an objective method of classifying patients based on skin color and sunburn sensitivity. The Cancer Genome Atlas (TCGA) is a method of determining the prognosis of patients with uveal melanoma based on genetic composition of the tumor. There is no literature studying the relationship of FST and TCGA groups. MATERIALS AND METHODS: Retrospective cohort study on 854 patients with uveal melanoma treated at a single tertiary ocular oncology center between April 2006 and June 2020, classified based on FST on a scale of I-VI and based on genetic analysis with TCGA classification on a scale of A, B, C, and D. Outcome measures included uveal melanoma-related metastasis and death per FST and TCGA group. RESULTS: Patients classified as FST I (compared to FST II and III-V) had higher odds of being TCGA group D (OR 2.34, p = 0.002). Patients classified as FST III-V (compared to FST I and II) had higher odds of being TCGA group B (OR 2.26, p = 0.002). Kaplan-Meier survival analysis showed no difference in melanoma-related metastasis or death comparing FST I vs. II vs. III-V within each TCGA group at 5, 10, and 15 years. CONCLUSIONS: Patients classified as FST I are more likely to have a higher grade melanoma on genetic testing whereas those classified as FST III-V show lower grade melanoma. Despite differences in tumor features and genetic profile with various FST, survival analysis at 5, 10, and 15 years revealed no difference in melanoma-related metastasis or death within each TCGA group per skin tone.

De novo frameshift mutation in YAP1 associated with bilateral uveal coloboma and microphthalmia.

BACKGROUND: Uveal colobomata are eye defects that result from failure of the optic fissure of the neuroectoderm-derived optic cup to close between weeks 5-7 of fetal life. Mutations in YAP1 have previously been linked to uveal coloboma. We present the clinical features and genetic basis of a one-year-old male with bilateral uveal colobomata. MATERIALS AND METHODS: Clinical features were gathered from an age-appropriate evaluation and retrospectively from clinical records. DNA samples were collected from the proband, his uncle (who also had coloboma), both parents, and one sibling. Whole-genome sequencing of the coding regions and intron-exon boundaries confirmed a mutation in the proband. These genetic findings were verified using the Sanger method of DNA sequencing. RESULTS: The proband is a male with congenital bilateral colobomata (iris/retina/nerve), reduced vision, nystagmus with null point, bilateral microcornea, right microphthalmia, possible mild right hemifacial microsomia, a tubular nose, possible spina bifida occulta, and astigmatism. Whole-genome sequencing confirmed a heterozygous YAP1 frameshift mutation NM_001130145.3:c.178dupG p.(Asp60GlyfsTer52) in the proband. This mutation was absent in all other tested family members. CONCLUSIONS: We report a de novo mutation in YAP1 that likely results in nonsense-mediated decay. Given the association with YAP1 haploinsufficiency and colobomatous microphthalmia, this novel variant provides a molecular diagnosis for the proband. Further insight into YAP1 mutations may have implications in the prevention/treatment of uveal coloboma and other syndromic disorders.

In vitro disease modeling of oculocutaneous albinism type 1 and 2 using human induced pluripotent stem cell-derived retinal pigment epithelium.

Oculocutaneous albinism (OCA) encompasses a set of autosomal recessive genetic conditions that affect pigmentation in the eye, skin, and hair. OCA patients display reduced best-corrected visual acuity, reduced to absent ocular pigmentation, abnormalities in fovea development, and/or abnormal decussation of optic nerve fibers. It has been hypothesized that improving eye pigmentation could prevent or rescue some of the vision defects. The goal of the present study was to develop an in vitro model for studying pigmentation defects in human retinal pigment epithelium (RPE). We developed a "disease in a dish" model for OCA1A and OCA2 types using induced pluripotent stem cells to generate RPE. The RPE is a monolayer of cells that are pigmented, polarized, and polygonal in shape, located between the neural retina and choroid, with an important role in vision. Here we show that RPE tissue derived in vitro from OCA patients recapitulates the pigmentation defects seen in albinism, while retaining the apical-basal polarity and normal polygonal morphology of the constituent RPE cells.

Short term outcomes of COVID-19 in lupus: Propensity score matched analysis from a nationwide multi-centric research network.

OBJECTIVES: To determine the severity and outcome of COVID-19 among individuals with lupus as compared to controls. The secondary objective was to identify the risk association of sex, race, presence of nephritis, and use of various immunomodulators with COVID-19 outcomes. METHODS: Retrospective data of individuals with lupus with and without COVID-19 between January 2020 to May 2021 was retrieved from the TriNetX. A one-to-one matched COVID-19 positive control was selected using propensity score(PS) matching. We assessed several outcomes, including all-cause mortality, hospitalisation, intensive care unit (ICU) admission, mechanical ventilation, severe COVID, acute kidney injury (AKI), Haemodialysis, acute respiratory distress syndrome (ARDS), ischemic stroke, venous thromboembolism (VTE) and sepsis were assessed. RESULTS: We identified 2140 SLE patients with COVID-19, 29,853 SLE without COVID-19 and 732,291controls. Mortality within 30 days of COVID-19 diagnosis was comparable among SLE and controls [RR-1.26; 95%CI-0.85,1.8]. SLE with COVID-19 had a higher risk of hospitalisation [RR-1.28; 95% CI 1.14-1.44], ICU admission [RR-1.35; 95% CI 1.01-1.83], mechanical ventilation [RR- 1.58 95% CI 1.07-2.33], stroke [RR-2.18; 95% CI 1.32,3.60], VTE [RR-2.22; 95% CI 1.57-03.12] and sepsis [RR-1.37; 95% CI 1.06-1.78].Individuals with SLE who contracted COVID-19 had higher mortality, hospitalisation, ICU admission, mechanical ventilation, AKI, VTE and sepsis (p < 0.001) compared to SLE without COVID-19. Males with SLE had a higher risk of AKI [RR-2.05; 95% CI 1.27-3.31] than females. Lupus nephritis was associated with higher risk of hospitalisation [RR-1.36; 95% CI 1.05-1.76], AKI [RR-2.32; 95% CI 1.50-3.59] and sepsis [RR-2.07; 95% CI-1.12-3.83]. CONCLUSION: The mortality of individuals with SLE due to COVID-19 is comparable to the general population but with higher risks of hospitalisation, ICU admission, mechanical ventilation, stroke, VTE and sepsis. The presence of nephritis increases the risk of AKI, thus probably increasing hospitalisation and sepsis.

Outcomes of COVID-19 in patients with rheumatoid arthritis: A multicenter research network study in the United States.

OBJECTIVES: To investigate outcomes of Coronavirus Disease-2019 (COVID-19) in patients with rheumatoid arthritis (RA) as compared to the general population. Additionally, outcomes were explored among RA patients stratified by sex, race, and medications use through sub-cohort analyses. METHODS: This comparative cohort study used a US multicenter research network (TriNetX) to extract data on all adult RA patients who were diagnosed with COVID-19, and adults without RA who were diagnosed with COVID-19 (comparative cohort) anytime from January 20, 2020 to April 11, 2021. COVID-19 outcomes were assessed within 30 days after its diagnosis. Baseline characteristics that included demographics and comorbidities were controlled in propensity score matching. RESULTS: A total of 9730 RA patients with COVID-19 and 656,979 non-RA with COVID-19 were identified. Before matching, the risk of all outcomes including mortality (RR: 2.11, 95%CI: 1.90 to 2.34), hospitalization (RR: 1.60, 1.55 to 1.66), intensive care unit-ICU admission (RR: 1.86, 1.71 to 2.05), mechanical ventilation (RR: 1.62, 1.44 to 1.82), severe COVID-19 (RR: 1.89, 1.74 to 2.06), acute kidney injury (RR: 2.13, 1.99 to 2.29), kidney replacement therapy/hemodialysis (RR: 1.40, 1.03 to 1.89), acute respiratory distress syndrome-ARDS (RR: 1.76, 1.53 to 2.02), ischemic stroke (RR: 2.62, 2.24 to 3.07), venous thromboembolism-VTE (RR: 2.30, 2.07 to 2.56), and sepsis (RR: 1.97, 1.81 to 2.13) was higher in RA compared to non-RA. After matching, the risks did not differ in both cohorts except for VTE (RR: 1.18, 1.01 to 1.38) and sepsis (RR: 1.27, 1.12 to 1.43), which were higher in the RA cohort. Male sex, black race, and glucocorticoid use increased the risk of adverse outcomes. The risk of hospitalization was higher in rituximab or interleukin 6 inhibitors (IL-6i) users compared to tumor necrosis factor inhibitors (TNFi) users, with no significant difference between Janus kinase inhibitors (JAKi) or abatacept users and TNFi users. CONCLUSION: This large cohort study of RA-COVID-19 found that the risk of all outcomes was higher in the RA compared to the non-RA cohort before matching, with no difference in the majority of outcomes after matching, implying the risk being attributed to adjusted factors. However, the risk of VTE and sepsis was higher in RA cohort even after matching, indicating RA as an independent risk factor. Male sex, black race, and glucocorticoid use were associated with adverse outcomes in RA with COVID-19. Rituximab or IL-6i users were associated with an increased risk of hospitalization compared to TNFi users.

Modeled Impacts of Chronic Wasting Disease on White-Tailed Deer in a Semi-Arid Environment.

White-tailed deer are a culturally and economically important game species in North America, especially in South Texas. The recent discovery of chronic wasting disease (CWD) in captive deer facilities in Texas has increased concern about the potential emergence of CWD in free-ranging deer. The concern is exacerbated because much of the South Texas region is a semi-arid environment with variable rainfall, where precipitation is strongly correlated with fawn recruitment. Further, the marginally productive rangelands, in combination with erratic fawn recruitment, results in populations that are frequently density-independent, and thus sensitive to additive mortality. It is unknown how a deer population in semi-arid regions would respond to the presence of CWD. We used long-term empirical datasets from a lightly harvested (2% annual harvest) population in conjunction with 3 prevalence growth rates from CWD afflicted areas (0.26%, 0.83%, and 2.3% increases per year) via a multi-stage partially deterministic model to simulate a deer population for 25 years under four scenarios: 1) without CWD and without harvest, 2) with CWD and without harvest, 3) with CWD and male harvest only, and 4) with CWD and harvest of both sexes. The modeled populations without CWD and without harvest averaged a 1.43% annual increase over 25 years; incorporation of 2% annual harvest of both sexes resulted in a stable population. The model with slowest CWD prevalence rate growth (0.26% annually) without harvest resulted in stable populations but the addition of 1% harvest resulted in population declines. Further, the male age structure in CWD models became skewed to younger age classes. We incorporated fawn:doe ratios from three CWD afflicted areas in Wisconsin and Wyoming into the model with 0.26% annual increase in prevalence and populations did not begin to decline until ~10%, ~16%, and ~26% of deer were harvested annually. Deer populations in variable environments rely on high adult survivorship to buffer the low and erratic fawn recruitment rates. The increase in additive mortality rates for adults via CWD negatively impacted simulated population trends to the extent that hunter opportunity would be greatly reduced. Our results improve understanding of the potential influences of CWD on deer populations in semi-arid environments with implications for deer managers, disease ecologists, and policy makers.