Racial and ethnic disparity in clinical outcomes among patients with confirmed COVID-19 infection in a large US electronic health record database.

BACKGROUND: Racial and ethnic minority groups have been disproportionately affected by the US coronavirus disease 2019 (COVID-19) pandemic; however, nationwide data on COVID-19 outcomes stratified by race/ethnicity and adjusted for clinical characteristics are sparse. This study analyzed the impacts of race/ethnicity on outcomes among US patients with COVID-19. METHODS: This was a retrospective observational study of patients with a confirmed COVID-19 diagnosis in the electronic health record from 01 February 2020 through 14 September 2020. Index encounter site, hospitalization, and mortality were assessed by race/ethnicity (Hispanic, non-Hispanic Black [Black], non-Hispanic White [White], non-Hispanic Asian [Asian], or Other/unknown). Associations between racial/ethnic categories and study outcomes adjusted for patient characteristics were evaluated using logistic regression. FINDINGS: Among 202,908 patients with confirmed COVID-19, patients from racial/ethnic minority groups were more likely than White patients to be hospitalized on initial presentation (Hispanic: adjusted odds ratio 1·690, 95% CI 1·620-1·763; Black: 1·810, 1·743-1·880; Asian: 1·503, 1·381-1·636) and during follow-up (Hispanic: 1·700, 1·638-1·764; Black: 1·578, 1·526-1·633; Asian: 1·391, 1·288-1·501). Among hospitalized patients, adjusted mortality risk was lower for Black patients (0·881, 0·809-0·959) but higher for Asian patients (1·205, 1·000-1·452). INTERPRETATION: Racial/ethnic minority patients with COVID-19 had more severe disease on initial presentation than White patients. Increased mortality risk was attenuated by hospitalization among Black patients but not Asian patients, indicating that outcome disparities may be mediated by distinct factors for different groups. In addition to enacting policies to facilitate equitable access to COVID-19-related care, further analyses of disaggregated population-level COVID-19 data are needed.

Fuchs' Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1.

Purpose: RNA toxicity from CTG trinucleotide repeat (TNR) expansion within noncoding DNA of the transcription factor 4 (TCF4) and DM1 protein kinase (DMPK) genes has been described in Fuchs' endothelial corneal dystrophy (FECD) and myotonic dystrophy, type 1 (DM1), respectively. We prospectively evaluated DM1 patients and their families for phenotypic FECD and report the analysis of CTG expansion in the TCF4 gene and DMPK expression in corneal endothelium. Methods: FECD grade was evaluated by slit lamp biomicroscopy in 26 participants from 14 families with DM1. CTG TNR length in TCF4 and DMPK was determined by a combination of Gene Scan and Southern blotting of peripheral blood leukocyte DNA. Results: FECD grade was 2 or higher in 5 (36%) of 14 probands, significantly greater than the general population (5%) (P < 0.001). FECD segregated with DM1; six of eight members of the largest family had both FECD and DM1, while the other two family members had neither disease. All DNA samples from 24 subjects, including four FECD-affected probands, were bi-allelic for nonexpanded TNR length in TCF4 (<40 repeats). Considering a 75% prevalence of TCF4 TNR expansion in FECD, the probability of four FECD probands lacking TNR expansion was 0.4%. Neither severity of DM1 nor DMPK TNR length predicted the presence of FECD in DM1 patients. Conclusions: FECD was common in DM1 families, and the diseases cosegregated. TCF4 TNR expansion was lacking in DM1 families. These findings support a hypothesis that DMPK TNR expansion contributes to clinical FECD.

Correction to: The diagnosis and treatment of primary vitreoretinal lymphoma: a review.

[This corrects the article DOI: 10.1186/s40942-018-0120-4.].

The diagnosis and treatment of primary vitreoretinal lymphoma: a review.

Background: To describe the recent diagnostic and treatment options for the most predominant form of primary vitreoretinal lymphoma (PVRL), namely diffuse large B cell lymphoma. This is mainly based on the experience at the Mayo Clinic as well as a partial review of the literature. MYD88 L265P mutation is seen in about 80% of cases; therefore, a polymerase chain reaction for this mutation helps in making the diagnosis that has been notoriously difficult to make. Local therapy using intravitreal methotrexate and rituximab has been very helpful in the treatment of the local disease. Systemic high-dose intravenous methotrexate is helpful in treating bilateral disease in conjunction with intravitreal therapy. Whether it is helpful in preventing or delaying the development of central nervous system lymphoma (CNSL) is still in dispute. If there is development of CNSL or recurrent ocular disease, alternatives to high-dose methotrexate under investigation include pomalidomide, stem cell transplantation, or ibrutinib, with or without local therapy. Vitrectomy alone might be helpful as a debulking procedure. Because of the risks of redevelopment of disease, local radiation should be given if other options are not possible. Aqueous levels of IL10 are helpful in following the redevelopment of local disease. Conclusion: Although PVRL is still a difficult disease to diagnose and treat, new advances are helping to make these easier. Larger collaborative studies will be helpful in determining better treatments.

Macular edema is a rare finding in untreated vitreoretinal lymphoma: small case series and review of the literature.

BACKGROUND: To determine the occurrence of macular edema (ME) in vitreoretinal lymphoma (VRL). METHODS: Retrospective analysis of 17 patients (31 eyes) with VRL. A review of the literature was done as well. RESULTS: Nine patients (15 eyes) had fluorescein angiography and/or optical coherence tomography at presentation. In the ME group (six eyes of four patients), three patients (five eyes) had prior chemotherapy and radiation. Excluding eyes with radiation retinopathy (three eyes), rate of ME was 25% (3/12). When two unirradiated fellow eyes of eyes with radiation retinopathy were also excluded, ME rate was 10% (1/10). Excluding the eyes with intraocular surgery, the rate of ME was 0%. In the group without ME (nine eyes of six patients), one patient (one eye) was treated with chemotherapy and radiation and three patients (five eyes) with chemotherapy. Review of the literature showed that the ME was found between 2 and 60% of cases, but most of the cases with ME had prior interventions. CONCLUSIONS: Macular edema in VRL is not uncommon but usually related to prior interventions. Macular edema as an initial presentation of VRL is rare.

USE OF FIBEROPTIC-GUIDED CO2 LASER IN THE TREATMENT OF UVEAL EFFUSION.

BACKGROUND/PURPOSE: To report a new technique for treating patients with uveal effusion syndrome by the fiberoptic-guided CO2 laser. METHODS: Interventional case report. A 74-year-old man presented with exudative detachment of the choroid secondary to uveal effusion syndrome. Partial-thickness sclerotomy and full-thickness sclerotomy were performed to treat the disease using a fiberoptic-guided CO2 laser. RESULTS: After the surgery, the patient's visual acuity improved and choroidal folds disappeared. CONCLUSION: This technique allows concomitant coagulation and cutting, thereby reducing the risk of bleeding and providing better depth control.

Ocular manifestations of tick-borne diseases.

Tick-borne illnesses are a significant disease burden worldwide. Diagnosis is challenging and requires a high level of clinical suspicion. Ocular manifestations reported in association with tick-borne disease are mostly as case reports and small case series because of the relative infrequency with which they occur; however, given the global nature of health care and increase in travel in the 21st century, it is important for ophthalmologists to be aware of ocular manifestations of these diseases because early diagnosis may reduce morbidity and mortality. Here, we review of the literature of tick-borne diseases with reported ophthalmic findings. All known human tick-borne diseases are discussed, including a brief description of the causative agent, region of endemicity, vector, systemic symptoms, and any reported eye findings. When possible, we also address the strength of the evidence for these ocular associations.

PREVALENCE OF MYD88 L265P MUTATION IN HISTOLOGICALLY PROVEN, DIFFUSE LARGE B-CELL VITREORETINAL LYMPHOMA.

PURPOSE: Myeloid differentiation primary response gene 88 (MYD88) is a universal adaptor protein in the innate immune system. When associated with a proline for leucine substitution mutation at position 265 (L265P), the protein becomes constitutively activated, amplifying the intracellular pro-inflammatory signal. Recently, we reported two cases of vitreoretinal lymphoma (VRL) that were positive for the mutation. The purpose of this study was to determine prevalence of the MYD88 L265P mutation in a larger series of VRL. METHODS: Retrospective chart review of 25 patients with histologically confirmed VRL evaluated at Mayo Clinic, Rochester, between January 2000 and March 2015. Paraffin-embedded blocks from the vitreous were submitted for polymerase chain reaction testing of the L265P mutation. RESULTS: The mutation was positive in 82.4% of all VRL cases and 86.7% of primary VRL cases. The minimum necessary DNA concentration needed for the polymerase chain reaction assay was 4.93 ng/mL. CONCLUSION: MYD88 gene analysis is a helpful ancillary tool for diagnosing VRL. It often requires fewer cells than flow cytometry or cytology and may be especially useful in early cases where a sufficient number of cells may not be available.

PRESUMED POSTERIOR UVEITIS RELATED TO EHRLICHIA EXPOSURE.

PURPOSE: To describe a case of posterior uveitis with retinal vasculitis related to Ehrlichia exposure. PATIENTS AND METHODS: Single case report of a 68-year-old woman with posterior uveitis, steroid-induced glaucoma, and retinal holes. RESULTS: Ehrlichia titers were elevated 4-fold (1:256; normal <1:64) with an otherwise normal laboratory workup. The patient's cystoid macular edema responded to sub-Tenon's triamcinolone and oral doxycycline. CONCLUSION: To our knowledge, this is the first case of posterior uveitis associated with Ehrlichia reported in humans.

Ocular Graft-Versus-Host Disease: A Review.

Hematopoietic stem cell transplantation is important in the management of several lymphoproliferative and bone marrow disorders. Graft-versus-host disease (GVHD) involves inflammatory manifestations that arise after transplant and can affect many organs. Ocular manifestations of GVHD are common, and eye care providers must understand this disease entity. The ocular surface is most commonly involved, but GVHD can affect all parts of the eye. Ocular GVHD can be relapsing and remitting, can decrease quality of life, and can be challenging to diagnose and adequately treat. The diagnostic criteria for and grading of ocular GVHD continue to evolve. This review aims to summarize current definitions, clinical findings, diagnostic criteria, and management of ocular GVHD. The care of patients with ocular GVHD requires a multidisciplinary approach.

Vitreoretinal lymphoma versus uveitis: cytokine profile and correlations.

PURPOSE: To compare the cytokine spectrum of vitreoretinal lymphoma to uveitis and correlate cytokine concentrations with disease activity. METHODS: Retrospective case series of 10 patients with vitreoretinal lymphoma and 7 patients with uveitis. Aqueous humor concentration of IFN-γ, TNF-α, TNF-ß, IL-1ra, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, MCP-1, G-CSF, GM-CSF, and VEGF-A was determined using a bead-based assay (Luminex). Variance between groups, correlation coefficients, and longitudinal behavior of cytokines were analyzed. RESULTS: No statistically significant difference in cytokines was found when comparing groups. IL-10 was positively correlated with IL-6 and MCP-1. IL-6 was positively correlated with G-CSF, IL-1ra, IL-8, and IL-10. A relationship between concentration of any cytokine, aside from IL-10, and disease activity was not found. CONCLUSION: IL-10 and IL-6 are good immunologic markers to be used as complementary diagnostic tools. IL-10 is the only IL that could be used for monitoring purposes.

Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

Safety of Tumor Necrosis Factor Inhibitors during Pregnancy and Breastfeeding.

PURPOSE: Tumor necrosis factor (TNF) inhibitors are useful in the treatment of numerous inflammatory and immunologic disorders. Since many of these conditions occur in women of childbearing age, safety during pregnancy and breastfeeding is of considerable importance. METHODS: This paper is a review of the literature on the safety of TNF inhibitors during pregnancy and breastfeeding published between 2001 and 2011. CONCLUSIONS: TNF inhibitors do not appear to be associated with a high risk of teratogenicity or intrauterine death. However, a small magnitude increase in risk cannot be ruled out given the paucity of data on the subject. Although TNF inhibitor use may be associated with a higher rate of preterm delivery, this may in fact be due to an active, underlying disease. Therefore, the decision to use these medications should be made on a case-by-case basis. If the disease cannot be managed with first line agents, TNF inhibitors may be helpful in reducing the number of disease exacerbations. Nevertheless, when using TNF inhibitors, it is prudent to discontinue treatment around the third trimester when transfer across the placenta is greatest and to restart postpartum.

Immune response in human cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Preliminary observations suggesting the presence of B and plasma cells and oligoclonality of immunoglobulin (Ig) G in cerebral cavernous malformations (CCM) have motivated a systematic study correlating the infiltration of the immune cells with clinical activity and antigen-triggered immune response in surgically excised lesions. METHODS: Infiltration of plasma, B, T, and human leukocyte antigen-DR-expressing cells and macrophages within 23 excised CCM was related to clinical activity. Relative amounts of Ig isotypes were determined. IgG clonality of mRNA from CCM was assessed by spectratyping, cloning, and sequencing. RESULTS: Infiltration of the immune cells ranged widely within CCM lesions, and cells were generally coexpressed with each other. Immune cell infiltration did not associate with recent bleeding and lesion growth. Significantly more B lymphocytes in CCM lesions were associated with venous anomaly. More T cells were present in solitary lesions. More T cells and less macrophages were present in CCM from younger subjects. IgG isotype was present in all CCM lesions. Most lesions also expressed IgM and IgA, with IgM predominance over IgA correlating with recent CCM growth. Oligoclonality was shown in IgG mRNA from CCM, but not from peripheral blood lymphocytes, with only 8 complementary-determining region 3 sequences observed among 134 clones from 2 CCM lesions. CONCLUSIONS: An antigen-directed oligoclonal IgG immune response is present within CCM lesions regardless of recent clinical activity. Apparent differences in immune response in younger patients and in lesions with recent growth will need confirmation in other series. The pathogenicity of oligoclonal immune response will require systematic hypothesis testing in recently available CCM murine models.