Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Painless Diplopia as Initial Presentation of Metastatic Lobular Breast Carcinoma

Intraorbital metastasis is a rare clinical finding present in 2-3% of cancer patients, with breast carcinoma accounting for up to 50% of cases. Orbital metastasis is primarily is diagnosed in patients with a known history of metastatic malignancy. We present a case of previously undiagnosed diffuse metastatic lobular carcinoma presenting as subtle binocular diplopia

Bilateral Acute Macular Neuroretinopathy after COVID-19 Vaccination and Infection

PURPOSE: To describe a case of acute macular neuroretinopathy (AMN) in a patient with recent COVID-19 vaccination and infection who demonstrated atypical features on presentation. OBSERVATIONS: A 64-year-old woman presented with central vision loss in both eyes (OU). She had recently received the Moderna COVID-19 vaccine and rapidly developed systemic symptoms. Testing revealed COVID-19 infection. Visual acuities were 20/200 OU and near-infrared reflectance revealed hypo-reflective lesions in the maculae OU, optical coherence tomography (OCT) showed outer nuclear layer thinning and ellipsoid zone disruption OU, and OCT-angiography showed flow voids in the deep capillary plexus and choriocapillaris OU, all consistent with AMN. She was treated with oral prednisone with subsequent mild vision improvement and persistent scotomas. DISCUSSION: COVID-19 associated AMN can present with a more severe clinical presentation than classically seen in AMN. Ischemic and inflammatory changes due to COVID-19 infection may contribute to this more advanced presentation

Antidrug Antibodies to Tumor Necrosis Factor α Inhibitors in Patients With Noninfectious Uveitis

IMPORTANCE: Tumor necrosis factor inhibitors (TNFis) can induce antidrug antibody (ADA) formation and loss of therapeutic response. However, the utility of ADA testing and the association between ADAs and treatment response in patients with noninfectious uveitis (NIU) is not well understood. OBJECTIVE: To assess the frequency of ADAs and their association with drug levels and clinical response in patients with NIU treated with adalimumab or infliximab. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study included patients diagnosed with NIU who received adalimumab or infliximab and underwent testing for serum drug level and ADAs at the National Eye Institute from September 2017 to July 2021. EXPOSURES: Serum drug level testing with reflex testing for ADA levels was performed. MAIN OUTCOMES AND MEASURES: The main outcome was the association between drug levels and ADAs, clinical response, and concurrent antimetabolite use in patients treated with TNFis for NIU. RESULTS: Of 54 patients included in the study, 42 received adalimumab (mean [SD] age, 43.6 [19.6] years; 25 [59.5%] female) and 12 received infliximab (mean [SD] age, 42.7 [20.4] years; 7 [58.3%] male). In the adalimumab group, mean (SD) drug level was 9.72 (6.82) μg/mL, mean (SD) ADA level was 84.2 (172.9) arbitrary units/mL, and ADA frequency was 35.7% (15 of 42 patients). Mean drug level was lower in those with ADAs compared with those without ADAs (mean [SD], 2.8 [2.6] μg/mL vs 13.6 [5.2] μg/mL; difference: 10.8 μg/mL; 95% CI, 8.3-13.2 μg/mL; P \u3c .001). There was a higher mean drug level with concurrent antimetabolite use compared with monotherapy (mean [SD], 11.0 [7.3] μg/mL vs 6.8 [4.5] μg/mL; difference: -4.2 μg/mL; 95% CI, -8.7 to 0.2 μg/mL; P = .06). Multivariable modeling showed that a 1-arbitrary unit increase in ADAs was associated with a -0.02 μg/mL (95% CI, -0.01 to -0.34 μg/mL) difference in mean drug level (P \u3c .001). Favorable clinical response was associated with a threshold drug level above 2.7 μg/mL or an antibody level below 15.2 μg/mL. The mean (SD) drug level in the infliximab group was 27.02 (18.15) μg/mL, and no ADAs were detected. CONCLUSIONS AND RELEVANCE: In this study, 35.7% of adalimumab-treated patients with NIU had ADAs. The presence of ADAs was associated with lower drug levels, and higher ADA levels were associated with increased risk of TNFi treatment failure. Although limited by the retrospective design, our results suggest that therapeutic drug monitoring may be considered among patients experiencing therapy failure to help exclude ADAs as a potential cause of treatment failure

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\u27s 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 \u3c 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

Bilateral Exudative Retinal Detachments and Panuveitis in a Patient with Multiple Myeloma

PURPOSE: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). CASE REPORT: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. CONCLUSION: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM

A comparative approach to testing hypotheses for the evolution of sex-biased dispersal in bean beetles

Understanding the selective forces that shape dispersal strategies is a fundamental goal of evolutionary ecology and is increasingly important in changing, human-altered environments. Sex-biased dispersal (SBD) is common in dioecious taxa, and understanding variation in the direction and magnitude of SBD across taxa has been a persistent challenge. We took a comparative, laboratory-based approach using 16 groups (species or strains) of bean beetles (generaﾠAcanthoscelides,ﾠCallosobruchus, andﾠZabrotes, including 10 strains of one species) to test two predictions that emerge from dominant hypotheses for the evolution of SBD: (1) groups that suffer greater costs of inbreeding should exhibit greater SBD in favor of either sex (inbreeding avoidance hypothesis) and (2) groups with stronger local mate competition should exhibit greater male bias in dispersal (kin competition avoidance hypothesis). We used laboratory experiments to quantify SBD in crawling dispersal, the fitness effects of inbreeding, and the degree of polygyny (number of female mates per male), a proxy for local mate competition. While we found that both polygyny and male-biased dispersal were common across bean beetle groups, consistent with the kin competition avoidance hypothesis, quantitative relationships between trait values did not support the predictions. Across groups, there was no significant association between SBD and effects of inbreeding nor SBD and degree of polygyny, using either raw values or phylogenetically independent contrasts. We discuss possible limitations of our experimental approach for detecting the predicted relationships, as well as reasons why single-factor hypotheses may be too simplistic to explain the evolution of SBD

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study

© 2018, American College of Medical Genetics and Genomics. Purpose: Osteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI. Methods: Using data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves. Results: In children, the median z-scores for height in OI types I, III, and IV were −0.66, −6.91, and −2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was −4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P \u3c 0.001), age, bisphosphonate use, and rodding (P \u3c 0.05). Conclusion: From the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves