Outpatient management of patients presenting with venous thromboembolism: Retrospective cohort study at 11 community hospitals.

A gap exists between clinical practice guidelines and real-world practice. We aim to investigate hospital admissions among patients presenting to emergency departments of 11 hospitals with venous thromboembolism (VTE). Eligible patients' first emergency department VTE visit were retrospectively collected between 2013 and 2018 from electronic medical records (EMR). Patients were categorized at low risk of VTE complications if they were diagnosed with deep vein thrombosis (DVT) of the leg or if they were diagnosed with pulmonary embolism (PE) and had a PE score index < 85. Multivariable logistic regression models were constructed to measure the adjusted odds ratios (OR) and 95% confidence intervals (CI) of hospital admissions before and after clinical practice guidelines were updated to recommend outpatient management of DVT and PE with low risk of complications. A total of 13,677 patients were included in the analysis, of which 55% were diagnosed with DVT. Mean age was 65  ±  17 years, 54% were females, and 62% were Caucasian. Overall, 9281 patients were categorized at low risk VTE complications, of whom 77% were admitted for in-hospital management. The rate of in-hospital management declined from 81% in 2013 to 73% in 2018. Patients visiting emergency departments between 2016 and 2018 (post-guidelines) were equally likely to be admitted compared to patients visiting the emergency departments between 2013 and 2015 (pre-guidelines; OR = 0.99; 95% CI: 0.88, 1.11). Results from this real-world study indicate that most low-risk VTE patients are admitted for in-hospital management, despite recommendations in clinical practice guidelines.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

PHARMACOKINETIC STUDY OF INTRAVITREAL AFLIBERCEPT IN HUMANS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the half-life of aflibercept in aqueous humor after a single intravitreal injection in patients with neovascular age-related macular degeneration. METHODS: Prospective, noncomparative, interventional case series of five eyes with neovascular age-related macular degeneration naive to anti-vascular endothelial growth factor therapy were enrolled and treated with intravitreal aflibercept. At baseline, best-corrected visual acuity, optical coherence tomography imaging, and aqueous humor (treatment eye) and blood/plasma samples were taken. Patients underwent best-corrected visual acuity, optical coherence tomography imaging, and sampling of aqueous humor from the eye and blood/plasma at six additional post-treatment time points of 4 hours and Days 1, 3, 7, 14, and 28. Concentrations of aflibercept were quantified using an enzyme-linked immunosorbent assay. RESULTS: Median peak concentration (Cmax) of free aflibercept in the aqueous was 122 mg/L. The median half-life of free aflibercept was 11 days in the eye. In plasma, the concentrations of free aflibercept were low and transient, reaching undetectable levels during the first week after injection, and undetectable in all patients at time points beyond 7 days. CONCLUSION: The pharmacokinetic profile in the aqueous humor described here together with the previously reported affinity of aflibercept for vascular endothelial growth factor is consistent with and adds to our understanding for the duration of its clinical efficacy.

Management of macular edema due to central retinal vein occlusion - The role of aflibercept.

Central retinal vein occlusion (CRVO) can cause vision loss. The pathogenesis of CRVO involves a thrombus formation leading to increased retinal capillary pressure, increased vascular permeability, and possibly retinal neovascularization. Vision loss due to CRVO is commonly caused by macular edema. Multiple treatment modalities have been used to treat macular edema. Currently, the most common therapy used is intravitreal inhibition of vascular endothelial growth factor (VEGF). The three most widely used agents are aflibercept, bevacizumab, and ranibizumab and they are effective at blocking VEGF. In addition, intraocular steroids can be used to treat macular edema. This review will briefly cover the treatment options and discuss in greater detail the efficacy and safety of aflibercept.

Combined systemic and ocular chemotherapy for anterior segment metastasis of systemic mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature. FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and fibrin. The AC cells stained positively for CD20. The iris was thickened and coated with lymphoma cells. Iris neovascularization was present. Given extensive systemic and ocular involvement, the patient was given combination chemotherapy with systemic ibrutinib and intravitreal injections of methotrexate and rituximab. The disease response was monitored using multimodal imaging, including anterior segment optical coherence tomography and ultrasound biomicroscopy. Following combination of systemic and intraocular chemotherapy, there was a marked decrease in the ocular tumor load and the systemic disease. CONCLUSIONS: Combination therapy with intravitreal injections of chemotherapeutic agents targeting monoclonal B-cell population and novel systemic agents may help to achieve remission in anterior segment metastasis of aggressive subtypes of NHL such as blastic variant of MCL. Multimodal imaging may assist in the management of these cases.

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development.

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described.

Potential role of lampalizumab for treatment of geographic atrophy.

The purpose of this article is to review the pathways underlying age-related macular degeneration and potential therapeutic targets, focusing on the complement pathway and the recent MAHALO Phase II trial of the investigational drug lampalizumab. This trial was the first to have shown positive results for the treatment of geographic atrophy in age-related macular degeneration. It has potential as a future treatment, and is currently undergoing a Phase III trial.

Clinical phenotypes and prognostic full-field electroretinographic findings in Stargardt disease.

PURPOSE: To investigate the relationships between clinical and full-field electroretinographic (ERG) findings and progressive loss of visual function in Stargardt disease. DESIGN: Retrospective cohort study. METHODS: We performed a retrospective review of data from 198 patients with Stargardt disease. Measures of visual function over time, including visual acuity, quantified Goldmann visual fields, and full-field ERG data were recorded. Data were analyzed using SAS statistical software. Subgroup analyses were performed on 148 patients with ERG phenotypic data, 46 patients with longitudinal visual field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or more mutations). RESULTS: Of 46 patients with longitudinal visual field data, 8 patients with faster central scotoma progression rates had significantly worse scotopic B-wave amplitudes at their initial assessment than 20 patients with stable scotomata (P = .014) and were more likely to have atrophy beyond the arcades (P = .047). Overall, 47.3% of patients exhibited abnormal ERG results, with rod-cone dysfunction in 14.2% of patients, cone-rod dysfunction in 17.6% of patients, and isolated cone dysfunction in 15.5% of patients. Abnormal values in certain ERG parameters were associated significantly with (maximum-stimulation A- and B-wave amplitudes) or tended toward (photopic and scotopic B-wave amplitudes) a higher mean rate of central scotoma progression compared with those patients with normal ERG values. Scotoma size and ERG parameters differed significantly between those with a single mutation versus those with multiple mutations. CONCLUSIONS: Full-field ERG examination provides clinically relevant information regarding the severity of Stargardt disease, likelihood of central scotoma expansion, and visual acuity deterioration. Patients also may exhibit an isolated cone dystrophy on ERG examination.

Treatment of ocular graft-versus-host disease with topical cyclosporine 0.05%.

PURPOSE: To evaluate the efficacy of topical cyclosporine-A 0.05% (CsA) in the treatment of dry eye syndrome in ocular graft-versus-host disease after bone marrow transplantation (BMT) of hematopoietic stem cells. METHODS: One-hundred five patients were enrolled in a retrospective, comparative, interventional case series. Eighty-one patients received topical CsA starting 1 month before BMT (treatment group), and 24 patients did not receive CsA until at least 6 months after the transplantation (control group). Mean follow-up time was 17.5 ± 11.0 months (range: 6.0-49.0 months). Clinical history, ocular surface disease index questionnaire, slit-lamp examination, lissamine green and fluorescein staining of the ocular surface, tear breakup time, and Schirmer test with topical anesthesia were obtained to create a composite dry eye-grading score. RESULTS: Dry eye symptoms were significantly more severe in the control group at 3 months, 1 year, and 2 years (P < 0.05). There was no correlation with type of stem cell transplant (related vs. unrelated donor), presenting indication for BMT, or concurrent systemic immunosuppressive medications. CONCLUSIONS: Pre-BMT initiation of topical CsA may reduce the inflammatory response in the lacrimal glands that may be responsible for the development of post-BMT keratitis sicca.

RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa.

OBJECTIVES: To assess the phenotype of patients with X-linked retinitis pigmentosa (XLRP) with RP2 mutations and to correlate the findings with their genotype. METHODS: Six hundred eleven patients with RP were screened for RP2 mutations. From this screen, 18 patients with RP2 mutations were evaluated clinically with standardized electroretinography, Goldmann visual fields, and ocular examinations. In addition, 7 well-documented cases from the literature were used to augment genotype-phenotype correlations. RESULTS: Of 11 boys younger than 12 years, 10 (91%) had macular involvement and 9 (82%) had best-corrected visual acuity worse than 20/50. Two boys from different families (aged 8 and 12 years) displayed a choroideremia-like fundus, and 9 boys (82%) were myopic (mean error, -7.97 diopters [D]). Of 10 patients with electroretinography data, 9 demonstrated severe rod-cone dysfunction. All 3 female carriers had macular atrophy in 1 or both eyes and were myopic (mean, -6.23 D). All 9 nonsense and frameshift and 5 of 7 missense mutations (71%) resulted in severe clinical presentations. CONCLUSIONS: Screening of the RP2 gene should be prioritized in patients younger than 16 years characterized by X-linked inheritance, decreased best-corrected visual acuity (eg, >20/40), high myopia, and early-onset macular atrophy. Patients exhibiting a choroideremia-like fundus without choroideremia gene mutations should also be screened for RP2 mutations. CLINICAL RELEVANCE: An identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.

Peripapillary dark choroid ring as a helpful diagnostic sign in advanced stargardt disease.

PURPOSE: To investigate the prevalence of a peripapillary dark choroid ring on fluorescein angiography (FA) and the associated clinical features in patients with Stargardt disease. DESIGN: Retrospective review of 135 patients with Stargardt disease. METHODS: The presence or absence of a peripapillary dark choroid ring on FA was noted and was compared with patient demographics and clinical features. RESULTS: Thirty-seven percent (50/135) had a peripapillary dark choroid ring on FA. When evaluated in subgroups, this sign was present in 41% (9/22) of patients with 2 causative ABCA4 mutations, in 28% (5/18) of patients with 1 causative ABCA4 mutation and a clinical diagnosis of Stargardt disease, and in 38% (36/95) of patients with a clinical diagnosis of Stargardt disease pending mutational analysis. Ninety-four percent (44/47) of patients for whom mutational testing confirmed the presence of ABCA4 mutations demonstrated a dark choroid sign. The peripapillary dark choroid ring sign was associated with diffuse flecks (P < .001), worse logarithm of the minimal angle of resolution visual acuity (P = .03), larger central scotoma size (P = .0146), and the presence of complete macular atrophy (P = .0017) compared with patients without this sign. CONCLUSIONS: The presence of a peripapillary dark choroid ring on FA should prompt further evaluation for Stargardt disease by examination of peripheral retinal FA images for a dark choroid sign, followed by subsequent ABCA4 mutation screening.

Fate maps of neural crest and mesoderm in the mammalian eye.

PURPOSE: Structures derived from periocular mesenchyme arise by complex interactions between neural crest and mesoderm. Defects in development or function of structures derived from periocular mesenchyme result in debilitating vision loss, including glaucoma. The determination of long-term fates for neural crest and mesoderm in mammals has been inhibited by the lack of suitable marking systems. In the present study, the first long-term fate maps are presented for neural crest and mesoderm in a mammalian eye. METHODS: Complementary binary genetic approaches were used to mark indelibly the neural crest and mesoderm in the developing eye. Component one is a transgene expressing Cre recombinase under the control of an appropriate tissue-specific promoter. The second component is the conditional Cre reporter R26R, which is activated by the Cre recombinase expressed from the transgene. Lineage-marked cells were counterstained for expression of key transcription factors. RESULTS: The results established that fates of neural crest and mesoderm in mice were similar to but not identical with those in birds. They also showed that five early transcription factor genes are expressed in unique patterns in fate-marked neural crest and mesoderm during early ocular development. CONCLUSIONS: The data provide essential new information toward understanding the complex interactions required for normal development and function of the mammalian eye. The results also underscore the importance of confirming neural crest and mesoderm fates in a model mammalian system. The complementary systems used in this study should be useful for studying the respective cell fates in other organ systems.