-
Genetics in Medicine : Official Journal... Mar 2022This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases. (Review)
Review
PURPOSE
This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.
METHODS
This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.
RESULTS
This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.
CONCLUSION
There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.
Topics: Color Vision Defects; Genetic Therapy; Humans; Optic Nerve Diseases; Retina; Retinal Dystrophies
PubMed: 34906485
DOI: 10.1016/j.gim.2021.10.013 -
PloS One 2024To establish the effects of anterior chamber inflammation (ACI) on the corneal endothelium parameters and central corneal thickness (CCT). (Meta-Analysis)
Meta-Analysis
PURPOSE
To establish the effects of anterior chamber inflammation (ACI) on the corneal endothelium parameters and central corneal thickness (CCT).
METHODS
We conducted a comprehensive literature review using medical databases (PubMed, EMBASE, VHL, and medRxiv) on March 8, 2023, for studies that included patients with ACI who had undergone specular microscopy or pachymetry. Case series with >10 patients, cross-sectional, case-control, and cohort studies were included. The risk of bias was assessed using CLARITY tools and validated scales such as those by Hassan Murad et al. and Hoy et al. A narrative synthesis and a quantitative standardized mean difference meta-analysis, I2 heterogeneity assessment, and publication bias tests were conducted. The study was registered in PROSPERO (CRD42023420148) and approved by the Universidad del Rosario ethical committee (DVO005 2277- CV1712).
RESULTS
Thirty-four studies, encompassing 1,388 eyes with ACI, were included. Compared with healthy controls, overall, ACI eyes show significant mean differences in endothelial parameters (endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX)) (P < 0.05). In the subgroup analysis compared with healthy controls, both active and chronic-recurrent ACI demonstrated a reduced ECD. An increased CV was observed in active, inactive, and chronic-recurrent ACI. Lower HEX was evident in inactive, acute, and chronic-recurrent ACI, while both active and acute ACI exhibited high CCT.
CONCLUSION
ACI leads to significant alterations in endothelial parameters and CCT. The primary contributors to these changes are increased IOP, uveitis duration, and intraocular surgeries. Further studies are needed to explore the impact of ACI etiology on the endothelium, potential biases in IOP measurements during acute ACI episodes, and the potential necessity for monitoring the endothelial parameters and CCT in patients with chronic ACI.
Topics: Humans; Endothelium, Corneal; Cross-Sectional Studies; Anterior Chamber; Inflammation; Correlation of Data
PubMed: 38181008
DOI: 10.1371/journal.pone.0296784 -
Minerva Ginecologica Oct 2020Behcet's disease (BD) is a rare inflammatory, multisystemic, autoimmune disorder with unknown origin. BD is included in vasculitic disorders with a more frequent onset...
INTRODUCTION
Behcet's disease (BD) is a rare inflammatory, multisystemic, autoimmune disorder with unknown origin. BD is included in vasculitic disorders with a more frequent onset characterized by oral and genital ulcers associated with eye inflammation. However, BD has several clinical manifestations, and the most fearful complication is thrombotic involvement. BD occurs mainly in women of childbearing age, therefore it is important to identify the potential risks of pregnancy on the mother and fetus.
EVIDENCE ACQUISITION
The aim of our review is to identify, through the study of existing literature, the possible consequences of pregnancy on the course of this disease, the potential risks for the mother and fetus in gestation period and in puerperium, in order to identify a correct pregnancy management in patient affected by BD.
EVIDENCE SYNTHESIS
Currently, there are few studies that have analyzed the consequences of the disease on the course of pregnancy and pregnancy on the activity of the pathology. Some authors believe that pregnancy may worsen the symptoms of the disease, while others may even improve the course. Many authors believe that thromboembolic events are the main problems for which focus attention on these patients, both in pregnancy and in puerperium. Different opinions exist about pregnancy complications and neonatal outcomes, although events such as abortion, intrauterine growth restriction and C-section appear to have a higher incidence in BD patients.
CONCLUSIONS
There are no contraindications for the onset of pregnancy in BD patients. In most cases pregnancy can improve the course of the disease. However, in view of the potential adverse events, a thorough follow-up of the pregnancy is necessary in order to minimize any risks to the mother and fetus.
Topics: Abortion, Spontaneous; Behcet Syndrome; Female; Humans; Infant, Newborn; Postpartum Period; Pregnancy; Pregnancy Complications; Retrospective Studies
PubMed: 32403914
DOI: 10.23736/S0026-4784.20.04564-5 -
Current Opinion in Rheumatology Jan 2023Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent...
PURPOSE OF THE REVIEW
Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent advances in the role of Treg and interleukin (IL)-10 in the pathogenesis and treatment of systemic vasculitis, including giant cell arteritis (GCA), Takayasu arteritis, Behçet's disease, antineutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV), and cryoglobulinemia associated vasculitis.
RECENT FINDINGS
Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Decreased peripheral blood frequencies of Treg are described in all vasculitis when compared to healthy donors. Altered Treg functions are reported in GCA, Takayasu arteritis, AAV, and Behçet's disease with different mechanisms proposed. Treatment with biologics, and sometimes other immunosuppressants, may restore Treg frequencies and/or immune activity with significant differences in active disease or disease in remission in several systemic vasculitis. IL-10 is elevated in GCA, AAV, cryoglobulinemia associated vasculitis. In Behçet's disease, IL-10 is decreased in peripheral blood and elevated in saliva. In Takayasu arteritis, IL-10 levels were essentially elevated in patients' vessel wall. Several new therapeutic approaches targeting Treg and Il-10 (low dose IL-2, CAR Treg…) are developed to treat patients with systemic vasculitis.
SUMMARY
Treg and IL-10 play a central role in the regulation of inflammation in vasculitis and new targeting approaches are emerging.
Topics: Humans; T-Lymphocytes, Regulatory; Interleukin-10; Behcet Syndrome; Giant Cell Arteritis; Takayasu Arteritis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 36508306
DOI: 10.1097/BOR.0000000000000915 -
Annales de Dermatologie Et de... Dec 2016Answering the question « what's new in internal medecine in 2016? » is very challenging. We used 3 methods of article selection to reduce the selection bias: 3... (Review)
Review
Answering the question « what's new in internal medecine in 2016? » is very challenging. We used 3 methods of article selection to reduce the selection bias: 3 authors, a systematic review of the articles discussed in the weekly bibliographic meeting of our unit (Dermatology department, Saint-Louis Hospital, Paris, France) and a selection of the best articles by several internal medecine practitioners in Paris. Eleven « hot topics » were analyzed: i/lowering cholesterol level but not blood blessure has a significant impact on cardiovascular morbi-mortality in cardiovascular intermediate risk patients; ii/the « treat to treat target » is efficient in psoriatic arthritis; iii/ a genotype/ phenotype correlation favors the separation of ileal Crohn's disease, colonic Crohn's disease and ulcerative colitis; iv/ tocilizumab treatment (anti-IL-6 monoclonal antibody ) is very efficient in giant cell arteritis and slightly efficient in systemic sclerosis; v/ combination therapy using methotrexate plus steroids compared with steroids alone becomes the « gold standard » treatment for juvenile dermatomyositis; vi/ dupilumab treatment (antibody blocking IL-4 and IL-13 receptors) is not only efficient in atopic dermatitis but also in asthma; vii/ think of eosinophilic oesophagitis in a patient with atopic dermatitis and dypshagia or food impaction; viii/ genetic A2 protein dysfunction induces NF-kB hyperactivation and an autoinflammatory disorder with features similar to Behcet's disease; ix/ no new biotherapies have shown high efficacy in systemic lupus erythematosus; x/ nanoparticles loaded with autoantigens induce Tregs and Bregs and may be a promising therapeutic option to treat auto-immune disease in the future; xi/ ipilimumab treatment (anti-CTLA4 antibody, immune checkpoint inhibitor) may induce complete remission in acute myeloid leukemia patients relapsing after haematological stem cell transplantation. Year 2016 is full of great discoveries in internal medicine keeping the dermatologist brain fully open minded.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antihypertensive Agents; Antineoplastic Agents, Immunological; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Behcet Syndrome; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammatory Bowel Diseases; Internal Medicine; Ipilimumab; Skin Diseases
PubMed: 29429506
DOI: 10.1016/S0151-9638(18)30046-2 -
The Journal of International Medical... May 2023To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease.
METHODS
In this systematic review and meta-analysis, the research question was designed using the 'Population, Intervention, Comparator, and Outcomes' (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence.
RESULTS
Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years.
CONCLUSION
Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet's disease.
Topics: Humans; Adult; Infliximab; Behcet Syndrome; Antibodies, Monoclonal; Tumor Necrosis Factor-alpha; Necrosis
PubMed: 37203384
DOI: 10.1177/03000605231169895 -
Canadian Journal of Ophthalmology.... Feb 2019Acute lymphoblastic leukemia (ALL) relapse implies a poor prognosis and demands emergency treatment. Leukemic infiltration of the anterior segment can masquerade as...
Acute lymphoblastic leukemia (ALL) relapse implies a poor prognosis and demands emergency treatment. Leukemic infiltration of the anterior segment can masquerade as intraocular inflammation; a high index of suspicion for this complication is essential. We describe a case of ocular relapse in a 2-year-old male on maintenance therapy for ALL. A systematic review of all known cases of similar leukemic infiltration of the anterior segment of the eye in ALL was performed. A total of 106 patients in 43 reports described leukemic infiltration of the eye as an initial presentation of ALL or relapse. Ocular relapse may be the first visible manifestation of systemic disease, with concurrent disease in the CNS, bone marrow, or testes. Prognosis for ALL patients with ocular relapse is poor, with death after initial presentation reported as early as 16 days. Patients with a history of ALL presenting with any sign of ocular inflammation should be assessed for relapse and leukemic infiltration. As soon as a diagnosis of relapse has been confirmed, appropriate leukemia therapy should be initiated.
Topics: Anterior Eye Segment; Child, Preschool; Humans; Leukemic Infiltration; Male; Microscopy, Acoustic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Uveitis
PubMed: 30851770
DOI: 10.1016/j.jcjo.2018.02.016 -
The Cochrane Database of Systematic... Aug 2020Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30% of these visits. Blunt trauma frequently leads to traumatic iridocyclitis, thus causing anterior uveitis. Iridocyclitis frequently causes tearing, photophobia, eye pain, and vision loss. These symptoms are a result of the inflammatory processes and ciliary spasms to iris muscles and sphincter. The inflammatory process is usually managed with topical corticosteroids, while the ciliary spasm is blunted by dilating the pupils with topical mydriatic agents, an adjuvant therapy. However, the effectiveness of mydriatic agents has not been quantified in terms of reduction of ocular pain and visual acuity loss.
OBJECTIVES
To evaluate the effectiveness and safety of topical mydriatics as adjunctive therapy to topical corticosteroids for traumatic iridocyclitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Trials Register (2019, issue 6); Ovid MEDLINE; Embase.com; Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus; PubMed; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 12 June 2019.
SELECTION CRITERIA
We planned to include randomized controlled trials (RCTs) that compared topical mydriatic agents in conjunction with topical corticosteroid therapy versus topical corticosteroids alone, in participants with traumatic iridocyclitis.
DATA COLLECTION AND ANALYSIS
Two review authors (JH, MK) independently screened titles and abstracts, then full-text reports, against eligibility criteria. We planned to have two authors independently extract data from included studies. We resolved differences in opinion by discussion.
MAIN RESULTS
There were no eligible RCTs that compared the interventions of interest in people with traumatic iridocyclitis.
AUTHORS' CONCLUSIONS
We did not find any evidence from RCTs about the efficacy of topical mydriatic agents as an adjunctive therapy with topical corticosteroids for treating traumatic iridocyclitis. In the absence of these types of studies, we cannot draw any firm conclusions. Controlled trials that compare the combined use of topical mydriatic agents and corticosteroid drops against standard corticosteroid drops alone, in people with traumatic iridocyclitis are required. These may provide evidence about the efficacy and risk of topical mydriatic drops as adjuvant therapy for traumatic iridocyclitis.
PubMed: 35659470
DOI: 10.1002/14651858.CD013260.pub2 -
The British Journal of Ophthalmology Aug 2020Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD...
BACKGROUND
Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD manifestations.
OBJECTIVE
To review the evidence base for biologics in the treatment of ocular BD.
METHODS
Systematic literature search was made using exploded key words-Behçet's, ocular, biologics in MEDLINE, Cochrane library, Database of Abstracts Reviews and Effects, Clinical Trials.gov, Science Direct and Google Scholar. There was no limitation on region, language or date (Search updated 16th October 2018). Literature retrieval was restricted to randomised controlled trials (RCTs) of biologics.
RESULTS
Of 237 papers retrieved, eight met the inclusion criteria. RCTs on interferon alpha 2a (INF-α 2a), adalimumab, secukinumab, gevokizumab, rituximab and daclizumab were retrieved (two for adalimumab and gevokizumab). The outcome measures were not met for secukinumab, daclizumab and gevokizumab. Rituximab and INF-α 2a showed promising preliminary results but sufficiently powered RCTs are needed to provide adequate evidence of efficacy. The RCTs on adalimumab did not evaluate efficacy for BD uveitis specifically, hence are of limited value for this review.
CONCLUSION
Some biologics show promise in treating BD uveitis, but more RCTs are needed for firm conclusions about efficacy. A phase IV study or, registry of adalimumab could provide data on its efficacy in BD uveitis compared to other forms.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Behcet Syndrome; Biological Factors; Biological Therapy; Daclizumab; Humans; Interferon-alpha; Rituximab; Uveitis
PubMed: 31676596
DOI: 10.1136/bjophthalmol-2019-314154 -
Journal of Digestive Diseases Feb 2021Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions. Evidence regarding mucosal healing for the prognosis of intestinal BD is scarce. The aim of this systematic review and meta-analysis was to determine the association between mucosal healing and long-term outcomes of patients with intestinal BD.
METHODS
Relevant studies were identified in a comprehensive search of PubMed, Cochrane Library, and EMBASE databases. Studies reporting long-term outcomes of mucosal healing in patients with intestinal BD were included. Pooled risk ratio (RR) and 95% confidence interval (CI) for disease recurrence and surgery were calculated using the Mantel-Haenszel random-effects models. Heterogeneity among the eligible studies was evaluated using the Q test and I statistics.
RESULTS
Of the 4785 studies initially identified, 8 were finally included. The pooled RR for the association between mucosal healing and disease recurrence was 0.41 (95% CI 0.30-0.57, P < 0.001). For the association between mucosal healing and the risk of surgery, the pooled RR was 0.33 (95% CI 0.17-0.63, P < 0.001). Confounding factors were adjusted in one study, whereas other studies only reported a crude association between mucosal healing and long-term outcomes without adjustment.
CONCLUSIONS
Mucosal healing is associated with a decreased risk of recurrence and surgery in intestinal BD. However, more studies are required given a small number of currently eligible studies and insufficient adjustment for confounding factors.
Topics: Behcet Syndrome; Humans; Intestinal Diseases; Intestines; Prognosis; Stomatitis, Aphthous
PubMed: 33314672
DOI: 10.1111/1751-2980.12965