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PloS One 2024Immune-mediated conjunctivitis is a prevalent ocular ailment characterized by inflammation and immune reactions in the conjunctiva. However, the precise causes and...
BACKGROUND
Immune-mediated conjunctivitis is a prevalent ocular ailment characterized by inflammation and immune reactions in the conjunctiva. However, the precise causes and therapeutic approaches for this condition remain the main focus for numerous ophthalmological specialists. Recently, accumulating evidence from human and mouse experiments has demonstrated the critical involvement of the NLRP3 inflammasome, IL-1β, and IL-18 in the development of allergic diseases. Targeting specific NLRP3 inflammasome and its related inhibitors may hold potential as therapeutic agents for immunologic conjunctivitis. Despite this, there has been no systematic review specifically addressing the treatment of immunologic conjunctivitis related to NLRP3. Therefore, this study aims to conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCTs) on NLRP3-related treatments for immunologic conjunctivitis patients, with the goal of evaluating their efficacy and safety.
METHODS
We will conduct a comprehensive search for relevant studies on NLRP3 inflammasome inhibitors or NLRP3-related treatments for immunologic conjunctivitis in various databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang. The search will encompass studies from their respective inception dates to July 2023. A meta-analysis will be performed using data extracted from eligible randomized controlled trials (RCTs), focusing on the clinical manifestations of immunologic conjunctivitis, levels of NLRP3-related factors in serum or tear samples, quality of life outcomes, and adverse events. Review Manager 5.4.1 software will be employed for the meta-analysis, and the results will be analyzed using either random-effects or fixed-effects models, depending on the presence of heterogeneity. The reliability and quality of evidence will be evaluated using the Grading of Recommendations, Development, and Evaluation (GRADE) system.
RESULTS
The findings of this study will yield robust and high-quality evidence regarding the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. This evidence will contribute significantly to our understanding of the potential benefits and risks associated with such treatments and will assist healthcare professionals in making informed decisions regarding the management of immunologic conjunctivitis.
CONCLUSION
This study represents the first comprehensive meta-analysis aiming to evaluate the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. The findings from this study will provide valuable evidence to guide clinical management strategies for this disease. The results are anticipated to significantly contribute to the understanding of the therapeutic potential and safety profile of NLRP3-related treatments, offering valuable insights for healthcare professionals involved in the care of patients with immunologic conjunctivitis.
TRIAL REGISTRATION
Systematic review registration: PROSPERO with registration number CRD42023437076.
Topics: Animals; Humans; Conjunctivitis; Inflammasomes; Meta-Analysis as Topic; NLR Family, Pyrin Domain-Containing 3 Protein; Randomized Controlled Trials as Topic; Research Design; Systematic Reviews as Topic
PubMed: 38277371
DOI: 10.1371/journal.pone.0296994 -
PloS One 2024To assess the differential association of myopia with major non-communicable ocular diseases in an African clinical cohort.
OBJECTIVE
To assess the differential association of myopia with major non-communicable ocular diseases in an African clinical cohort.
METHODS
A five-year hospital-based retrospective study of myopia cases. Patients' folders, Optical Coherence Tomography scans, and fundus photographs were reviewed for the abstraction of relevant data. Only records that employed recognized standards and classification systems for diagnosing and staging the various ocular conditions were included. Demographic characteristics, non-cycloplegic objective refractive findings, and non-communicable eye diseases were retrieved from the records. Myopia-associated risk factors were then determined using logistic regression and correlation.
RESULTS
Some 16018 patients (32027 eyes) met the inclusion criteria for at least one eye comprising 50.8% males (n = 8137) and 49.2% females (n = 7881). The mean age of the patients was 43.14 ± 17.88 years (range: 2-98 years). The mean spherical equivalent± Standard deviation for myopia was -2.30±3.23 DS (range: -0.50 to -25DS). Binary logistic regression analysis showed that myopic eyes had a higher odd of AC (OR, 0.53; 95% CI, 0.50-0.57), POAG (OR, 6.0; 95% CI, 5.26-6.82), DR (OR, 10.70; 95% CI, 3.91-29.27) and cataracts (OR, 20; 95% CI, 15.32-26.20) but not dry eye (OR, 0.74, 95% CI, 0.68-0.81), macular degeneration and pterygium (OR, 0.36; 95% CI, 0.32-0.40).
CONCLUSION
Africans with myopia are more at risk of developing allergic conjunctivitis, cataracts, POAG, and DR but not for dry eye, macular degeneration, and pterygium.
Topics: Male; Female; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Pterygium; Retrospective Studies; Ghana; Myopia; Refraction, Ocular; Macular Degeneration; Cataract; Conjunctiva; Glaucoma, Open-Angle
PubMed: 38236924
DOI: 10.1371/journal.pone.0297052 -
BMC Infectious Diseases Jan 2024Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk...
BACKGROUND
Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient.
CASE PRESENTATION
A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders.
CONCLUSIONS
High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.
Topics: Female; Humans; Middle Aged; Autoantibodies; Immunologic Deficiency Syndromes; Interferon-gamma; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Tuberculosis
PubMed: 38216890
DOI: 10.1186/s12879-024-09003-x -
Cell Stem Cell Feb 2024The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their...
The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13 exposure increases goblet and tuft cell differentiation and drastically modifies the conjunctiva secretome. Human NGFR+ basal cells are identified as bipotent conjunctiva stem cells. Conjunctival cultures can be infected by herpes simplex virus 1 (HSV1), human adenovirus 8 (hAdV8), and SARS-CoV-2. HSV1 infection was reversed by acyclovir addition, whereas hAdV8 infection, which lacks an approved drug therapy, was inhibited by cidofovir. We document transcriptional programs induced by HSV1 and hAdV8. Finally, conjunctival organoids can be transplanted. Together, human conjunctiva organoid cultures enable the study of conjunctival (patho)-physiology.
Topics: Humans; Mice; Animals; Conjunctiva; Goblet Cells; Epithelium; Interleukin-13; Homeostasis; Organoids
PubMed: 38215738
DOI: 10.1016/j.stem.2023.12.008 -
Cureus Nov 2023Ptosis in pediatrics is commonly attributed to neurological causes. Rarely, chronic inflammation of the upper eyelid and the formation of giant papillary conjunctivitis...
Ptosis in pediatrics is commonly attributed to neurological causes. Rarely, chronic inflammation of the upper eyelid and the formation of giant papillary conjunctivitis due to vernal keratoconjunctivitis (VKC) may lead to ptosis. In this case report, we present an eight-year-old girl with conjunctivitis who was referred to a pediatric neurology service for evaluation of ptosis. She presented with progressive left-eye ptosis while experiencing allergic conjunctivitis. Her neurological exam showed non-fatigable ptosis with a negative curtain sign. The rest of the neurology examination was normal. She tested negative for anti-MuSK and anti-Ach. The orbital MRI was unremarkable. Further detailed examination by an ophthalmologist showed severe VKC with a giant papillary formation that had led to mechanical ptosis.
PubMed: 38161878
DOI: 10.7759/cureus.49731 -
Indian Journal of Ophthalmology Jan 2024
Topics: Humans; Keratoconus; Conjunctivitis, Allergic; Corneal Transplantation; Glucocorticoids; Steroids; Keratoplasty, Penetrating; Treatment Outcome
PubMed: 38131596
DOI: 10.4103/IJO.IJO_1799_23 -
Indian Journal of Ophthalmology Jan 2024This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of...
PURPOSE
This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of patients presenting at a multitier ophthalmology hospital network.
METHODS
This cross-sectional hospital-based study included the data of 2,384,523 patients presenting between January 2012 and March 2020. Data were collected from an EMR system. Patients with a clinical diagnosis of KCN in at least one eye were included in this study. Univariate analysis was performed to identify the prevalence of KCN. A multiple logistic regression analysis was performed using R software (version 3.5.1), and the odds ratios are reported.
RESULTS
Data were obtained for 14,749 (0.62%) patients with 27,703 eyes diagnosed with KCN and used for the analysis. The median age of the patients was 22 (inter-quartile range (IQR): 17-27). In total, 76.64% of adults (odds ratio = 8.77; P = <0.001) were affected the most. The majority of patients were male (61.25%), and bilateral (87.83%) affliction was the most common presentation. A significant proportion of the patients were students (63.98%). Most eyes had mild or no visual impairment (<20/70; 61.42%). Corneal signs included ectasia (41.35%), Fleischer ring (44.52%), prominent corneal nerves (45.75%), corneal scarring (13.60%), Vogts striae (18.97%), and hydrops (0.71%). Only 7.85% showed an association with allergic conjunctivitis. A contact lens clinic assessment was administered to 47.87% of patients. Overall, 10.23% of the eyes affected with KCN underwent a surgical procedure. the most common surgery was collagen cross-linking (8.05%), followed by deep anterior lamellar keratoplasty (1.13%) and penetrating keratoplasty (0.88%).
CONCLUSION
KCN is usually bilateral and predominantly affects males. It commonly presents in the second and third decade of life, and only a tenth of the affected eyes require surgical treatment.
Topics: Adult; Humans; Male; Female; Keratoconus; Cross-Sectional Studies; Data Science; Visual Acuity; India; Prevalence; Retrospective Studies
PubMed: 38131579
DOI: 10.4103/IJO.IJO_1190_23 -
Clinical Ophthalmology (Auckland, N.Z.) 2023There is an unmet need for new treatments for allergic conjunctivitis. (Clinical Trial)
Clinical Trial
PURPOSE
There is an unmet need for new treatments for allergic conjunctivitis.
OBJECTIVE
To assess the activity of reproxalap, a novel reactive aldehyde species modulator, in a real-world model of seasonal allergen exposure.
METHODS
The INVIGORATE Trial, a prospective, quadruple-masked, vehicle-controlled, crossover, sequence-randomized Phase 3 trial, tested the efficacy of reproxalap in adults with a history of moderate to severe allergic conjunctivitis, ragweed pollen allergy, and allergen chamber-induced ocular itching and redness. Patients were randomly assigned (1:1) to receive 0.25% reproxalap ophthalmic solution or vehicle, followed by a 2-week washout period before crossing over to the other test article. The primary endpoint was ocular itching from 110 to 210 minutes after chamber entry; the key secondary endpoint was ocular redness over the chamber duration (0-4 scales for both endpoints).
RESULTS
Of the 95 randomly assigned patients, 89 completed all visits (reproxalap to vehicle: n = 46; vehicle to reproxalap: n = 43). Primary and key secondary endpoints were met: reproxalap significantly reduced ocular itching (mean [SE]: -0.50 [0.03], p < 0.001) and redness (-0.14 [0.01], p < 0.001) relative to vehicle. Responder analyses confirmed the clinical relevance of both end points. Reproxalap was safe and well tolerated. No clinically significant changes in safety assessments were observed. No serious or severe treatment-emergent adverse events (TEAEs) were reported. The most commonly reported TEAE was mild and transient installation site irritation after reproxalap versus vehicle administration.
CONCLUSION
In this well-controlled allergen chamber trial, reproxalap was statistically superior to vehicle across typical symptoms and signs of allergic conjunctivitis.
TRIAL REGISTRATION
NCT04207736.
PubMed: 38105911
DOI: 10.2147/OPTH.S441009 -
Frontiers in Molecular Neuroscience 2023The prevalence of allergic conjunctivitis in itchy eyes has increased constantly worldwide owing to environmental pollution. Currently, anti-allergic and antihistaminic...
The prevalence of allergic conjunctivitis in itchy eyes has increased constantly worldwide owing to environmental pollution. Currently, anti-allergic and antihistaminic eye drops are used; however, there are many unknown aspects about the neural circuits that transmit itchy eyes. We focused on the gastrin-releasing peptide (GRP) and GRP receptor (GRPR), which are reportedly involved in itch transmission in the spinal somatosensory system, to determine whether the GRP system is involved in itch neurotransmission of the eyes in the trigeminal sensory system. First, the instillation of itch mediators, such as histamine (His) and non-histaminergic itch mediator chloroquine (CQ), exhibited concentration-dependent high levels of eye scratching behavior, with a significant sex differences observed in the case of His. Histological analysis revealed that His and CQ significantly increased the neural activity of GRPR-expressing neurons in the caudal part of the spinal trigeminal nucleus of the medulla oblongata in GRPR transgenic mice. We administered a GRPR antagonist or bombesin-saporin to ablate GRPR-expressing neurons, followed by His or CQ instillation, and observed a decrease in CQ-induced eye-scratching behavior in the toxin experiments. Intracisternal administration of neuromedin C (NMC), a GRPR agonist, resulted in dose-dependent excessive facial scratching behavior, despite the absence of an itch stimulus on the face. To our knowledge, this is the first study to demonstrate that non-histaminergic itchy eyes were transmitted centrally via GRPR-expressing neurons in the trigeminal sensory system, and that NMC in the medulla oblongata evoked facial itching.
PubMed: 38098939
DOI: 10.3389/fnmol.2023.1280024