Humanized Mice for the Study of Immuno-Oncology De La Rochere, Philippe; Guil-Luna, Silvia; Decaudin, Didier ...
Trends in immunology,
September 2018, 2018-09-00, 20180901, Letnik:
39, Številka:
9
Journal Article
Recenzirano
Immunotherapy is revolutionizing cancer treatment; however, complete responses are achieved in only a small fraction of patients and tumor types. Thus, there is an urgent need for predictive ...preclinical models to drive rational immunotherapeutic drug development, treatment combinations, and to minimize failures in clinical trials. Humanized mouse models (HIS) have been developed to study and modulate the interactions between immune components and tumors of human origin. In this review, we discuss recent advances in the ‘humanization’ of mouse models to improve the quality of human immune cell reconstitution. We also highlight new insights into the basic mechanisms, and provide a preclinical evaluation of onco-immunotherapies, as well as the limitations thereof, which constitute drivers for the improvement of the models to increase their translational power.
Cancer immunotherapy has given impressive clinical responses but only in a minority of patients and only in certain cancer indications. Thus, predictive preclinical models are needed to drive rational immunotherapeutic drug development and minimize failures in clinical trials.
HIS, comprising immunodeficient host mice and human immune and tumor cells, recapitulate the interactions between immune components and tumors of human origin.
Limitations of HIS models include the development of xenograft-versus-host disease and incomplete reconstitution of certain human immune subpopulations.
HIS models have allowed the evaluation of onco-immunotherapies, including cellular and antibody-based immunotherapies.
Understanding the caveats of HIS mice and the increasing genetic optimizations are leading to improved models with heightened translational power.
Purpose
To investigate the clinical profile and visual outcomes of infectious endophthalmitis in children at a single tertiary hospital in France, and propose an evidence-based protocol for ...management.
Methods
This is a retrospective monocentric study that involved children with a history of endophthalmitis between January 2008 and January 2020. The clinical characteristics, etiology, microbiological spectrum from aqueous/vitreous tab, anatomical and visual outcomes, and management were analyzed. The Fischer and chi-square tests were used in the statistical evaluation.
Results
Twenty-six children were eligible for inclusion. The mean patients age at presentation was 4.2 years (range, 8 days–14.3 years). With regard to etiology, patients were divided into
posttraumatic group
(
n
= 7 (26.9%)),
postoperative group
(
n
= 15 (57.7%)),
endogenous group
(
n
= 3 (11.5%)), and
infectious corneal ulcer group
(
n
= 1 (3.9%)). Time-to-onset of symptoms was highest in children ≤ 3 years old and in the
postoperative subgroup
who had at least one glaucoma procedure. Microbiology results showed growth in 12/26 (46.2%). The most common microorganism identified was
Streptococcus pneumoniae
(5/12 (41.7%)). The antibiotic regimen varied depending on age, organism, and sensitivities. The final visual outcomes were 20/200 or better in 11/26 (42.3%) eyes, and 13/26 (50.0%) eyes had no light perception. Twelve of twenty-six (46.2%) eyes ended up with phthisis bulbi.
Conclusion
Pediatric endophthalmitis is a rare but devastating condition with poor visual prognosis, requiring prompt recognition and treatment. Despite aggressive management with antibiotics and vitrectomy, the visual prognosis is generally poor. A protocol for management with an adapted systemic antibiotic therapy is proposed in order to improve outcomes.
Purpose
To describe and interpret the features of pachychoroid neovasculopathy (PNV) using optical coherence tomography angiography (OCTA) technique.
Methods
This is an observational case series of ...patients who presented with PNV. Best‐corrected visual acuity (BCVA), anterior segment examination, dilated funduscopic examination, infrared and autofluorescence fundus images and spectral‐domain optical coherence tomography (SD‐OCT; B‐scan, ‘en‐face’ and OCTA) were carried out for all patients. Choroid thickness was measured using enhanced depth imaging (EDI) mode. Colour fundus photographs, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were not performed systematically. Optical coherence tomography angiography (OCTA) features of PNV are described and interpreted.
Results
Five eyes of five patients with a mean age of 62.2 years (range, 53–73 years) presenting with PNV were analysed. They all presented pachychoroid pigment epitheliopathy (PPE) with choroidal thickening and dilated choroidal vessels as seen with EDI‐OCT. Fluorescein angiography (FFA) was performed in three patients showing multiple areas of retinal pigment epithelium atrophy and fundus lesions suggestive of chronic central serous chorioretinopathy. Indocyanine green angiography (ICGA) in one patient confirmed the presence of large choroidal veins and choroidal hyperpermeability seen beneath the area of the neovascular tissue. Two eyes had the appearance of polypoidal structures within the neovascular tissue, with the characteristic aspect of the polypoidal lesions on B‐scan and ‘en‐face’. Optical coherence tomography angiography (OCTA) showed the appearance of tangled filamentous vascular network in all eyes.
Conclusion
Optical coherence tomography angiography (OCTA) is a safe, highly sensitive and specific examination for the detection of type 1 neovascularization associated with PPE. Features are characteristic of tangled filamentous vessels overlying a focal area of thickened choroid.
Aim. The purpose of this study is to evaluate and compare the efficacy of 4 prostaglandin analogues (PGAs) and to determine the incidence of ocular surface disease in newly diagnosed, primary ...open-angle glaucoma (POAG) patients started on one of those 4 PGAs: bimatoprost (benzalkonium chloride, BAK, 0.3 mg/mL), latanoprost (BAK 0.2 mg/mL), travoprost (polyquad), and tafluprost (BAK-free). Patients and Methods. In this single-center, open-label trial, 32 patients newly diagnosed with POAG were randomly started on one of the four PGAs. All patients underwent a complete ophthalmological exam at presentation and at 1, 3, and 6 months of follow-up. Dry eye disease (DED) was assessed using the original Ocular Surface Disease Index (OSDI) questionnaire, in order to evaluate the impact of the drops on the quality of life of patients. Results. The mean age was 60.06 years ± 11.76. All four drugs equally and significantly reduced the intraocular pressure (IOP) with respect to the baseline IOP. There was a trend for a slightly greater reduction of IOP with bimatoprost, but the difference was not found to be statistically significant when compared to other PGAs. OSDI scores were significantly superior for travoprost (10.68 ± 5.73) compared to the other three drugs (p<0.05). Latanoprost caused the most significant eyelash growth and iris discoloration. Conjunctival hyperemia and superficial keratitis occurrence were similar in the four groups. Conclusion. All prostaglandin analogues equally and significantly reduce the IOP in patients with POAG. According to the results of the OSDI score, latanoprost seems to be the least tolerated among the four drugs.
Background: Acute macular neuroretinopathy (AMN) is an increasingly diagnosed disorder associated with several diseases. The aim of this study was to report the incidence of AMN cases diagnosed ...during the 2020 coronavirus disease 2019 (COVID-19) pandemic year in a French hospital, and to describe their different forms. Methods: All patients diagnosed between 2019 and 2020, in Paris Rothschild Foundation Hospital, with AMN, paracentral acute middle maculopathy (PAMM) and multiple evanescent white dot syndrome (MEWDS) were retrospectively collected using the software Ophtalmoquery® (Corilus, V1.86.0018, 9050 Gand, Belgium). Systemic and ophthalmological data from AMN patients were analyzed. Results: Eleven patients were diagnosed with AMN in 2020 vs. only one patient reported in 2019. The incidence of AMN significantly increased from 0.66/100,000 visits in 2019 to 8.97/100,000 visits in 2020 (p = 0.001), whereas the incidence of PAMM and MEWDS remained unchanged. Four (36%) of these AMN patients were tested for COVID-19 and received positive polymerase chain reaction (PCR) tests. Conclusions: The incidence of AMN cases increased significantly in our institution in 2020, which was the year of the COVID-19 pandemic. All AMN-tested patients received a positive COVID PCR test, suggesting a possible causative link. According to the different clinical presentations, AMN may reflect different severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pathogenic mechanisms.
Wilson's disease (WD) is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and accumulation in various tissues. Ocular ...findings are one of the hallmarks of the disease. Many ophthalmological manifestations have been described and new techniques are currently available to improve their diagnosis and to follow their evolution. We have performed a systematic PubMed search to summarize available data of the recent literature on the most frequent ophthalmological disorders associated with WD, and to discuss the newest techniques used for their detection and follow-up during treatment. In total, 49 articles were retained for this review. The most common ocular findings seen in WD patients are Kayser-Fleischer ring (KFR) and sunflower cataracts. Other ocular manifestations may involve retinal tissue, visual systems and eye mobility. Diagnosis and follow-up under decoppering treatment of these ocular findings are generally easily performed with slit-lamp examination (SLE). However, new techniques are available for the precocious detection of ocular findings due to WD and may be of great value for non-experimented ophthalmologists and non-ophthalmologists practitioners. Among those techniques, anterior segment optical coherence tomography (AS-OCT) and Scheimpflug imaging are discussed.
Objective
To evaluate the risk factors and outcomes of central retinal vein occlusion (CRVO) in young patients (< 40 years).
Methods
In this retrospective monocentric case series, we included young ...patients (<40 years) with CRVO. Patients’ medical files were analyzed focusing on demographic characteristics, suspected risk factors, ophthalmic work-up, visual acuity (VA), treatment, and outcomes.
Results
A total of 54 eyes of 52 patients were included. Central retinal vein occlusion was considered idiopathic in 13 patients (25%). The main risk factors identified were ocular hypertension (20.4%), inflammation (20.4%), high blood pressure (14.8%), and coagulation abnormality (11.1%). Final VA was lower in patients with high blood pressure and inflammation when compared to patients with no risk factor (
p
= 0.03 and 0.04, respectively). Intravitreal injections were needed in 23 eyes (42.6%) and 19 eyes (35.2%) received panretinal photocoagulation treatment.
Conclusion
Central retinal vein occlusion is frequently associated with risk factors in young patients (75% of patients). In addition to the usual factors found in older patients, such as ocular hypertension and high blood pressure, coagulation abnormality and inflammation were also among the risk factors identified. Young patients with CRVO should be evaluated for the presence of risk factors and patients with high blood pressure or inflammatory findings should be followed carefully since they have a worse outcome.
The aim of the study is to report on the indocyanine green angiography (ICGA) and OCT findings in patients hospitalized for severe COVID infection. In this observational prospective monocentric ...cohort study, we included patients hospitalized for severe COVID infection. The main outcomes were ICGA and OCT findings. A total of 14 patients with a mean age of 58.2 ± 11.4 years and a male predominance (9/14 patients; 64%) were included. The main ICGA findings included hypofluorescent spots in 19 eyes (68%), intervortex shunts in 10 eyes (36%), and characteristic "hemangioma-like" lesions in five eyes (18%). "Hemangioma-like" lesions were both unique and unilateral, and showed no washout on the late phase of the angiogram. The main OCT findings included focal choroidal thickening in seven eyes (25%), caverns in six eyes (21%) and paracentral acute middle maculopathy lesions in one eye (4%). All patients hospitalized for severe COVID infection had anomalies on ICGA and OCT. Lesions to both retinal and choroidal vasculature were found. These anomalies could be secondary to vascular involvement related directly or indirectly to the SARS-CoV2 virus.
The immune system is increasingly found to be involved in the development of several chronic illnesses, for which allopathic medicine has provided limited tools for treatment and especially ...prevention. In that context, it appears worthwhile to target the immune system in order to modulate the risk of certain chronic illnesses. Meanwhile, natural health products (NHPs) are generating renewed interest, particularly in the prevention and treatment of several chronic diseases. Over 20 scientists from fields related to immune function and NHPs were thus convened to establish the state of knowledge on these subjects and to explore future research directions. This review summarizes the result of discussions held during the symposium. It thus seeks to be thought provoking rather than to comprehensively cover such broad areas of research. Notably, a brief overview of the immune system is presented, including potentially useful targets and strategies to keep it in an equilibrated state, in order to prevent certain disorders. The pertinence and limitations of targeting the immune system to prevent chronic diseases is also discussed. The paper then discusses the usefulness and limitations of current experimental tools available to study the immune modulating effects of NHPs. Finally, a concise review of some of the most studied NHPs showing promising immunomodulatory activity is given, and avenues for future research are described.
Atypical Foveal Hypoplasia in Best Disease Moret, Emmanuelle; Lejoyeux, Raphaël; Bonnin, Sophie ...
Journal of personalized medicine,
02/2023, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
To determine the prevalence and characteristics of foveal hypoplasia (also called fovea plana) in patients with Best disease using spectral-domain (SD) optical coherence tomography (OCT) and ...OCT-angiography (OCT-A).
A retrospective observational study including patients diagnosed with Best disease.
Fifty-nine eyes of thirty-two patients (fifteen females (46.9%) and seventeen males (53.1%),
= 0.9) diagnosed with Best disease were included. Patients' eyes were categorized into two groups: Eyes with a fovea plana appearance ('FP group') and eyes without fovea plana appearance ('no FP group'), based on the foveal appearance on B-scan SD-OCT.
Cross-sectional OCT images were assessed for the persistence of inner retinal layers (IRL) and OCT-A was analyzed for the presence of a foveal avascular zone (FAZ), the size of which was determined when applicable.
Overall, 16 eyes (27.1%) of 9 patients had a fovea plana appearance ('FP group') with the persistence of IRL, and 43 eyes (72.9%) of 23 patients did not have fovea plana appearance ('no FP group'). Among FP eyes, OCT-A performed in 13 eyes showed bridging vessels through the FAZ in 100% of eyes with OCT-A. Using Thomas classification, 14 out of the 16 eyes with fovea plana (87.5%) had atypical foveal hypoplasia, and the 2 others (12.5%) had a grade 1b fovea plana.
In our series, foveal hypoplasia was present in 27.1% of patients with Best disease. OCT-A showed bridging vessels through the FAZ in all eyes. These findings highlight the microvascular changes associated with Best disease, which can be an early sign of the disease in patients with a family history.
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