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Clinical Ophthalmology (Auckland, N.Z.) 2024To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the... (Clinical Trial)
Clinical Trial
PURPOSE
To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the treatment of allergic conjunctivitis in a real-world model of allergen exposure.
METHODS
This was a prospective comparative trial. Adults with testing-confirmed bilateral allergic conjunctivitis received DEX in the more symptomatic eye and either LOT 2 times daily or OLO once daily for 30 days in the fellow eye. The primary outcome was patient preference for treatment. Clinical outcomes included ocular itching and hyperemia, lid swelling, and watering/tearing. Safety outcomes included intraocular pressure (IOP).
RESULTS
Thirty patients participated and completed the study. All received DEX in the eye with worse symptoms and 15 received LOT and the other 15 received OLO in the other eye. Patients preferred DEX (10/15; 66.7%) over LOT (4/15; 26.7%), with one patient having no preference (p = 0.0103). Patients had no preference between DEX (8/15; 53.3%) and OLO (6/15; 40%), with one patient having no preference (p = 0.1044). In the DEX/LOT cohort, ocular itching and hyperemia improved more with DEX than LOT (p ≤ 0.009), while in the DEX/OLO cohort, the DEX eyes showed greater improvement in conjunctival hyperemia (p < 0.0001) but not itching (p = 0.074). No between-group differences were seen in eyelid swelling or tearing/watering in either cohort. Mean change in IOP was similar between the DEX and LOT eyes (p = 0.4921), and mean IOP rose more in the DEX eyes than the OLO eyes (by <1 mmHg; p = 0.0403).
CONCLUSION
Overall, this real-world study demonstrated that the dexamethasone intracanalicular insert was as effective as a topical antihistamine/mast cell stabilizer and more effective than topical steroids in relieving the signs and symptoms of allergic conjunctivitis. This insert should be considered as an alternative to topical therapy for the treatment of allergic conjunctivitis.
PubMed: 38375441
DOI: 10.2147/OPTH.S440840 -
Die Ophthalmologie Mar 2024In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and... (Review)
Review
BACKGROUND
In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief.
OBJECTIVE
Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given.
MATERIAL AND METHODS
Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented.
RESULTS
In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC).
CONCLUSION
A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Tacrolimus; Immunologic Factors; Adjuvants, Immunologic; Ophthalmic Solutions
PubMed: 38363381
DOI: 10.1007/s00347-024-01996-9 -
Dermatology (Basel, Switzerland) 2024Atopic dermatitis (AD), a chronic type 2 inflammatory skin disease, is frequently associated with ocular surface diseases (OSD) which may appear or worsen under...
INTRODUCTION
Atopic dermatitis (AD), a chronic type 2 inflammatory skin disease, is frequently associated with ocular surface diseases (OSD) which may appear or worsen under anti-type 2-targeted treatments. However, the exact prevalence of OSD and the ophthalmology referral criteria remain ill-defined in AD patients before initiating such biotherapies. We aimed to characterize the prevalence, the nature and the factors related to OSD development in AD that may justify an ophthalmological management.
METHODS
A total of 98 consecutive AD inpatients without biological treatment were retrospectively included. These were systematically evaluated by an ophthalmologist during their dermatological care. Clinical and laboratory data were analysed to characterize OSD and their risk factors.
RESULTS
OSD were found in 83/98 AD patients (85%); mainly dry eye syndrome (64%, 63/98), allergic conjunctivitis (42%, 41/98), posterior (33%, 32/98), and anterior blepharitis (27%, 26/98). In AD patients without ocular symptoms, OSDs were also frequently found (63%, 12/19) and were mostly mild. Risk factors for OSD were history of allergic rhinitis, allergic sensitization, head and neck AD, ocular symptoms (foreign body sensation in the eye, burning, itching, photophobia), and total IgE level >3,000 kU/L.
CONCLUSION
The prevalence of OSD was high, even in asymptomatic patients. The risk factors identified may indicate the need for ophthalmological examination for therapeutic management, especially when biological agents targeting type 2 inflammation are considered.
Topics: Humans; Dermatitis, Atopic; Male; Female; Retrospective Studies; Adult; Middle Aged; Prevalence; Risk Factors; Dry Eye Syndromes; Conjunctivitis, Allergic; Young Adult; Blepharitis; Adolescent; Aged; Eye Diseases
PubMed: 38354719
DOI: 10.1159/000536233 -
The World Allergy Organization Journal Feb 2024The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis...
OBJECTIVE
The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding.
METHODS
Utilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results.
RESULTS
The TSMR analysis demonstrated MSAB increased the risks of CA (P = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (P = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (P <0.001, OR: 0.946, 95%CI: 0.918 to 0.974). MSAB still increased the risks of CA (P = 0.0497, OR: 1.013, 95%CI: 1.000017 to 1.026) and AD (P = 0.003, OR: 13.800, 95%CI: 2.490 to 269.246) after adjusting for breastfeeding. We observed no strong indication of a negative causality between MSAB and AC and AR.
CONCLUSION
Our findings provided robust evidence of the adverse effects of MSAB on offspring. We emphasized the urgency of smoking cessation around birth and the importance of breastfeeding even in smoking mothers.
PubMed: 38351904
DOI: 10.1016/j.waojou.2024.100875 -
Clinical Ophthalmology (Auckland, N.Z.) 2024A fixed-combination eye drop has several advantages over combination therapy, however, the intraocular pressure (IOP)-lowering efficacy and safety of the newly available...
PURPOSE
A fixed-combination eye drop has several advantages over combination therapy, however, the intraocular pressure (IOP)-lowering efficacy and safety of the newly available brimonidine + ripasudil fixed-combination (BRFC) eye drops after switching from brimonidine + ripasudil is yet to be established. Therefore, this study aimed to retrospectively investigate the 6-month safety, usability, and IOP-lowering efficacy of BRFC switched from brimonidine and ripasudil.
PATIENTS AND METHODS
Overall, 69 patients with primary open-angle glaucoma (69 eyes) receiving brimonidine + ripasudil were enrolled in this study. Brimonidine + ripasudil was discontinued, and treatment was switched to BRFC without a washout period. The IOP was compared before and at 3 and 6 months after switching to BRFC. The side effects, discontinued cases, and usability (a questionnaire survey) were also investigated.
RESULTS
The IOP was not significantly different after switching to BRFC (15.1 ± 3.3 mmHg at baseline, 15.9 ± 3.6 mmHg after 3 months, and 14.6 ± 3.3 mmHg after 6 months). Adverse reactions occurred in four patients (5.8%): allergic conjunctivitis, two patients; irritation, one patient; and blurred vision, one patient. Treatment was discontinued in five (7.2%) patients owing to allergic conjunctivitis, two patients; increased IOP, two patients; and blurred vision, one patient. In the questionnaire survey, 68 patients with eye pain, 67 with itching, 64 with conjunctival hyperemia, 64 with irritation, and 62 with blurred vision reported no change or improved conditions. Additionally, in response to the question regarding preferences for pre-treatment and fixed combinations, 14 participants (20.2%) favored pre-treatment, while 53 (76.8%) preferred fixed combinations.
CONCLUSION
The IOP was maintained for 6 months, with satisfactory safety and comfort of use, with BRFC switched from brimonidine and ripasudil.
PubMed: 38343903
DOI: 10.2147/OPTH.S446962 -
Translational Medicine @ UniSa 2023Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host...
Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host microbiota, a key player in the induction and maintenance of immunoregulatory circuits and tolerance. The increase of allergic diseases in the elderly is also related to additional factors, such as various comorbidities that may interfere with the development and the type of allergic reactions. Immunosenescence plays a central role in these reactions, altering microbiota responses and triggering inflammageing. In addition, in the elderly, there is a shift from Th1 to Th2 immunity, thus favoring allergic responses. A better understanding of the mechanisms responsible for immunosenescence and its effects on allergic inflammation will most certainly lead to improved therapies.
PubMed: 38343419
DOI: 10.37825/2239-9747.1046 -
International Ophthalmology Feb 2024This study aims to determine the efficacy and safety of accelerated corneal crosslinking in children with keratoconus.
PURPOSE
This study aims to determine the efficacy and safety of accelerated corneal crosslinking in children with keratoconus.
METHODS
The study enrolled 64 patients aged 16 years or younger, each contributing one eye for a total of 64 eyes for analysis. Participants underwent an accelerated form of corneal cross-linking with 15 min of ultraviolet A irradiation at a rate of 7 mW/cm, resulting in a cumulative energy dose of 5.4 J/cm. The primary outcome measures were best corrected visual acuity (BCVA) and corneal tomography at 6 and 12 months post-intervention. Parameters assessed included BCVA, spherical and cylindrical refraction, keratometry (K1 and K2), maximum keratometry (Kmax) and thinnest corneal thickness (TCT). These metrics were documented preoperatively and then again at 6 and 12 months postoperatively. In addition, any ocular or systemic conditions related to keratoconus were recorded for each participant.
RESULTS
The results showed an improvement in BCVA at 12 months after surgery. K1 showed a decrease at both post-operative follow-ups while K2 remained constant throughout the observation period. Kmax showed a notable decrease at the 12 month postoperative follow-up. Although the TCT showed an initial decrease, it reached a stable state after 12 months of crosslinking. Refractive values remained stable at all subsequent examinations. Notably, no complications such as corneal opacity, non-healing epithelial defects or corneal infections occurred during the follow-up period. The most common ocular comorbidity was allergic conjunctivitis (34.4%).
CONCLUSION
The findings suggest that accelerated corneal crosslinking treatment is effective in slowing or halting the progression of keratoconus. Furthermore, there were no persistent overt complications observed at 12 months after the procedure.
Topics: Humans; Child; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Visual Acuity; Corneal Topography; Follow-Up Studies; Cross-Linking Reagents; Collagen
PubMed: 38342827
DOI: 10.1007/s10792-024-02996-z -
Die Ophthalmologie Mar 2024Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often a challenge. (Review)
Review
BACKGROUND
Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often a challenge.
OBJECTIVE
Discussion on the epidemiology, new pathogenetic concepts, interesting clinical findings, diagnostic possibilities and new treatment options and their side effects in severe ocular allergies. Analysis of the presentation of VKC in the internet.
MATERIAL AND METHODS
Evaluation of recent review articles, original publications, and case reports on the topics of VKC and AKC over the past 5 years.
RESULTS
Ocular allergies have significantly increased over the last decades. Recent concepts discussed in the pathogenesis of VKC and AKC are the role of the local and gut microbiome as well as the influence of neuroinflammation. Keratoconus is significantly more common in patients with VKC and AKC compared to the normal population. It is associated with faster progression and a more severe course of disease. A conjunctival provocation test is only rarely necessary in the diagnosis of allergic conjunctivitis. Treatment of atopic dermatitis with dupilumab, an interleukin 4 receptor alpha (IL-4Ra) antagonist, can cause ocular side effects. Unfortunately, information available on the internet for patients and parents on the topic of VKC is sometimes dangerously incorrect.
CONCLUSION
From the abovementioned new pathogenetic concepts, preventive and personalized treatment options could be developed in the future. Keratoconus in AKC/VKC must be recognized and treated early. Official guidelines are now available for a standardized conjunctival provocation test in the diagnosis of allergic conjunctivitis. The unwanted ocular side effects of dupilumab are often difficult to discriminate from the actual underlying AKC and respond well to anti-inflammatory treatment. Patients with VKC must be informed about the incorrect information on the internet regarding their disease.
Topics: Humans; Conjunctivitis, Allergic; Keratoconus; Eye; Keratoconjunctivitis
PubMed: 38334798
DOI: 10.1007/s00347-024-01984-z -
Mucosal Immunology Apr 2024Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in...
Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1 sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1 sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.
Topics: Mice; Animals; Conjunctivitis, Allergic; Tumor Necrosis Factor-alpha; Conjunctiva; Eosinophils; Antineoplastic Agents; Inflammation; TRPV Cation Channels
PubMed: 38331094
DOI: 10.1016/j.mucimm.2024.02.001 -
Die Ophthalmologie Mar 2024Allergen-specific immunotherapy (AIT) is the only causal and disease-modifying treatment for immunoglobulin E (IgE)-mediated type I allergies. Regular exposure to the... (Review)
Review
Allergen-specific immunotherapy (AIT) is the only causal and disease-modifying treatment for immunoglobulin E (IgE)-mediated type I allergies. Regular exposure to the causative allergen results in an immunomodulatory effect by which the predominant T‑helper (Th) 2 lymphocyte response is shifted to a Th1 lymphocyte response and more allergen-specific blocking immunoglobulins are produced. The approval of substances for AIT is regulated by the Therapy Allergens Ordinance (TAV). There are subcutaneous and/or sublingual AITs for the following indications: allergic rhinitis, allergic conjunctivitis, allergic asthma and insect venom allergy. In this article the indications for allergic conjunctivitis are discussed in particular. Clinical symptoms and a relevant type 1 sensitization are the prerequisites for the indications for AIT. The assessment of the indications and carrying out an AIT should only be carried out by physicians who have been trained in allergology.
Topics: Humans; Conjunctivitis, Allergic; Desensitization, Immunologic; Rhinitis, Allergic; Allergens; Immunoglobulin E
PubMed: 38324025
DOI: 10.1007/s00347-024-01987-w