Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch.

Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunctiva, but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identified a subset of memory-type pathogenic Th2 cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin-gene-related peptide (CGRP) in the inflammatory conjunctiva using a single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacological blockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients with severe allergic conjunctivitis revealed ectopic lymphoid structure formation with the accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenic CD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axis directs severe itch with neuro-reconstruction in the inflammatory conjunctiva and is a potential therapeutic target for severe itch in allergic conjunctivitis.

The Relationship between Allergic Disease and Sexual Dysfunction: A Scoping Review.

INTRODUCTION: Sexual dysfunction (SD) and allergic disease are common health concerns worldwide and bear a potential relationship. This scoping review is conducted to analyze the currently available data regarding the associations between these two health issues. METHODS: A comprehensive literature search was performed in the databases of PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to retrieve studies that were published before January 2023. A narrative synthesis was conducted to analyze the effects of allergic diseases on SD based on the evaluation of the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF). RESULTS: Twelve observational studies were included after the selection process. The results generally suggested lower FSFI or IIEF scores in patients with asthma, allergic rhinitis, allergic rhinoconjunctivitis, and urticaria compared to the healthy control groups. The underlying factors of this relationship could be inflammation, psychological factors, hormonal changes, sleep disorders, sexual behavior-related allergic reactions, social economic status, and the use of medications. CONCLUSION: SD and allergic disease are interrelated based on the extant literature. This scoping review provides insights into the clinical implications of both entities, while more research studies are warranted to further elucidate this complex relationship.

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Ocular effects of eye cosmetic formulations.

OBJECTIVE: To study the ocular effects seen among eye cosmetic wearers in the Indian Population. METHODS: This cross-sectional study was conducted on female participants who had fulfilled the inclusion and exclusion criteria. A detailed history was obtained and thorough ophthalmic evaluation was done. Mann Whitney U test was used. Statistical analysis was done using IBM SPSS. p < .05 was taken as the level of statistical significance. RESULTS: Among a total of 225 participants in our study, the mean age was 24.23 ± 1.8, which comprised of young student females. Majority of the females used one eye cosmetic with Kajal (n = 156) being the most predominant. Most frequently encountered symptom upon using eye cosmetics was watering from eyes and ocular pain was the least encountered symptom. Anterior segment examination showed- allergic conjunctivitis and meibomian gland dysfunction being the most and least predominant, respectively. Our study highlights that Kajal predisposes the eyes to significant ocular morbidity with p = .039 for dry eye disease, p = .041 for allergic conjunctivitis, p = .036 for conjunctival pigmentation. Prolonged use of such formulations for more than 4 times a week (p = .046) or even daily (p = .031) for a duration of either 1-5 years (p = .033) or greater than 5 years (p = .027) was found to be statistically significant in causing ocular signs. Non removal of eye cosmetics at the end of the day was significant in causing allergic conjunctivitis (p = .035) and conjunctival pigmentation (p = .021). Plain tap water has been found to be the least effective technique in the removal of such ocular cosmetics with a statistical significance of p = .031 in causing ocular signs. CONCLUSIONS: Eye cosmetics are a significant contributor to the development of ocular surface diseases. Removal of products along with decreased usage seems to be a significant contributor in dampening unwanted adverse effects.

Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis.

The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive in situ gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive in situ gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121℃ for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.

Effect of atopic conditions on development and recurrences of infectious keratitis.

BACKGROUND: Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV). METHODS: This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR. RESULTS: Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025). CONCLUSIONS: Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.

Use of explainable AI on slit-lamp images of anterior surface of eyes to diagnose allergic conjunctival diseases.

BACKGROUND: Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis. METHODS: A dataset of 4942 slit-lamp images from 10 ophthalmological institutions across Japan were used as the image database. A sequential pipeline of segmentation AI was constructed to identify 12 clinical findings in 1038 images of seasonal and perennial allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and normal subjects. The performance of the pipeline was evaluated by determining its ability to obtain explainable results through the extraction of the findings. Its diagnostic accuracy was determined for 4 severity-based diagnosis classification of AC, AKC/VKC, GPC, and normal. RESULTS: Segmentation AI pipeline efficiently extracted crucial ACD indicators including conjunctival hyperemia, giant papillae, and shield ulcer, and offered interpretable insights. The AI pipeline diagnosis had a high diagnostic accuracy of 86.2%, and that of the board-certified ophthalmologists was 60.0%. The pipeline had a high classification performance, and the area under the curve (AUC) was 0.959 for AC, 0.905 for normal subjects, 0.847 for GPC, 0.829 for VKC, and 0.790 for AKC. CONCLUSIONS: An explainable AI model created by a comprehensive image database can be used for diagnosing ACDs with high degree of accuracy.

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.

Diagnostic approach and grading scheme for canine allergic conjunctivitis.

BACKGROUND: In humans, allergic conjunctivitis is a well described disease. In contrast, allergic conjunctivitis has not received much attention from the veterinary community so far. Canine allergic conjunctivitis (cAC) is one of the possible manifestations associated with canine atopic dermatitis (cAD), being often underdiagnosed and undertreated. Our aim is to contribute to disease characterization and clinical stagingfor cAC severity. RESULTS: A retrospective observational study including 122 dogs that underwent a complete ophthalmological and dermatological examinations and diagnosed with allergic conjunctivitis was conducted. A total of six ophthalmic clinical signs were considered for disease characterization and clinical staging: conjunctival hyperemia, chemosis, ocular pruritus, epiphora, seromucoid to mucopurulent discharge and keratitis, classified from 0 (absent) to 3 (severe). Scores comprised between 1-5 were considered mild, 6-10 moderate and 11-18 severe. The majority of dogs (64%) presented with moderate cAC followed by 24% of mild stages and only 12% of severe presentations. The severity of allergic conjunctivitis was not correlated to sex or age at the time of diagnosis and all presented with a bilateral form of the disease. Chemosis (84%), hyperemia (83%) and ocular pruritus (79%) was observed in 55% of the cases. Seromucoid to mucopurulent discharge (62%) and epiphora (69%) were less frequent, with keratitis being the least encountered clinical sign (15%). The degree of keratitis showed a positive correlation with both severity and chronicity of cAC (rho = 0.21-0.29, p ≤ 0.02)). Severity of cAD and cAD were not significantly correlated (p-value = 0.4). DISCUSSION AND CONCLUSION: The triad hyperemia, chemosis and ocular pruritus, already known in human medicine to be a reliable way of diagnosing human allergic conjunctivitis, also proved to be important in cAC Mild forms of the disease may pass unnoticed, ocular pruritus being hard to assess in canine patients.The proposed standardized diagnostic approach and novel grading scheme for cAC may be of value for both veterinary ophthalmologists and dermatologists, as well as general practitioners.

Bilastine 0.6% preservative-free eye drops, an effective once-daily treatment to reduce signs and symptoms of allergic conjunctivitis: A pooled analysis of two randomized clinical trials.

BACKGROUND AND OBJECTIVE: Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free, bilastine 0.6% eye drop formulation for the treatment of allergic conjunctivitis. METHODS: Two double-masked, vehicle controlled, clinical studies (a Phase 2 Dose Ranging Study and a Phase 3 Efficacy Study) were conducted to assess the efficacy of bilastine ophthalmic solution for the treatment of signs and symptoms of allergic conjunctivitis. Both studies used the Ora-CAC® Conjunctival Allergen Challenge (CAC) Model to allow observations of allergic responses under controlled conditions. Each study was analyzed separately and then combined to create an integrated dataset. RESULTS: Efficacy was achieved for the primary efficacy endpoint of ocular itching for three bilastine concentrations (0.2%, 0.4%, and 0.6%) at 15 minutes and 8 hours post-instillation and bilastine 0.6% ophthalmic solution was also efficacious at 16 hours post-instillation. Bilastine 0.6% ophthalmic solution demonstrated non-inferiority to ketotifen 0.025% at the onset of action. From the integrated data set, differences between vehicle and bilastine 0.6% were significant at all time points both at onset (15 minutes) and at a prolonged duration (16 hours) after instillation. CONCLUSION: This multi-trial assessment suggests that bilastine 0.6% ophthalmic solution is efficacious for the treatment of the signs and symptoms of allergic conjunctivitis, with a rapid and prolonged duration of action, and has a favorable safety profile. The added convenience of a once-a-day dosing regimen may contribute to patient adherence and improve their quality of life.