Amlodipine Ocular Delivery Restores Ferning Patterns and Reduces Intensity of Glycosylated Peak of Carrageenan-Induced Tear Fluid: An In-Silico Flexible Docking with IL-ß1.

BACKGROUND: The tear ferning test can be an easy clinical procedure for the evaluation and characterization of the ocular tear film. OBJECTIVE: The objective of this study was to examine the restoration of tear ferning patterns and reduction of glycosylation peak after amlodipine application in carrageenan-induced conjunctivitis. METHODS: At the rabbit's upper palpebral region, carrageenan was injected for cytokine-mediated conjunctivitis. Ferning pattern and glycosylation of the tear fluid were characterized using various instrumental analyses. The effect of amlodipine was also examined after ocular instillation and flexible docking studies. RESULTS: Optical microscopy showed a disrupted ferning of the tear collected from the inflamed eye. FTIR of the induced tear fluid exhibited peaks within 1000-1200 cm-1, which might be due to the protein glycosylation absent in the normal tear spectrogram. The glycosylation peak reduced significantly in the tear sample collected from the amlodipine-treated group. Corresponding energy dispersive analysis showed the presence of sulphur, indicating protein leakage from the lacrimal gland in the induced group. The disappearance of sulphur from the treated group indicated its remedial effect. The flexible docking studies revealed a stronger binding mode of amlodipine with Interleukin-1ß (IL-1ß). The reduction in the intensity of the glycosylated peak and the restoration offering are probably due to suppression of IL-1ß. CONCLUSION: This study may be helpful in obtaining primary information for drug discovery to be effective against IL-1ß and proving tear fluid as a novel diagnostic biomarker.

Association between short-term ozone exposure and allergic conjunctivitis in China: A multi-city case-crossover study.

Short-term exposure to ozone has been linked to multiple allergic diseases, but the relationship between ozone exposure and allergic conjunctivitis (AC) remains unclear. This study aimed to investigate the association between short-term exposure to ozone and the risk of AC. We conducted a time-stratified case-crossover study across five Chinese cities from 2014 to 2022. Daily outpatient visit records for AC were identified in five hospitals using either the diagnosis name or ICD-10 code H10.1. Data on air pollution and meteorological conditions were also collected. We first examined the city-specific association between short-term ozone exposure and AC using conditional logistic regression. A random-effects meta-analysis was then conducted to obtain overall estimates. During the study period, 130,093 outpatient visits for AC occurred, with 58.8% (76,482) being male and 41.2% (53,611) female. A one-standard-deviation (SD) increase in ozone was associated with an 8.3% increase (95% CI: 3.8%, 13.0%) in AC outpatient visits. Similar positive associations were observed when adjusting for other pollutants (PM2.5, CO, SO2 and NO2) in two-pollutant and multi-pollutant models. Furthermore, the positive association remained consistent when using mixed-effects regression models or further adjusting for meteorological conditions. In addition, no effect modification of the AC-ozone association by sex, age and season was apparent. This study provides evidence supporting a positive association between short-term ozone exposure and AC risk in China. This highlights the potential value of mitigating ozone pollution to reduce the risk of ocular surface disorders.

Effect of antihistamine-releasing contact lenses on ocular symptoms and treatment behavior in patients with seasonal allergic conjunctivitis: A retrospective study.

Purpose: This study aimed to compare subjective allergic conjunctivitis symptoms and anti-allergic eye drop use patterns between antihistamine-releasing contact lens users and daily disposable soft contact lens users during Japan's hay fever season. Methods: This web-based retrospective cohort study included daily disposable soft contact lens or antihistamine-releasing contact lens users with a history of seasonal allergic conjunctivitis who regularly used daily disposable soft contact lenses since the previous year. The total ocular symptom score (range 0-20) based on 5-item questionnaire scores and time from the start of the hay fever season to the initiation of anti-allergic eye drop treatment were compared between antihistamine-releasing contact lens users and daily disposable soft contact lens users. Results: The study included 24 participants: 17 using daily disposable soft contact lenses and 7 using antihistamine-releasing contact lenses. Antihistamine-releasing contact lens users experienced a greater reduction in total ocular symptom score from 2021 to 2022 compared with daily disposable soft contact lens users (mean total ocular symptom score [standard deviation]: daily disposable soft contact lens: -0.65 [1.4], antihistamine-releasing contact lens: -4.7 [3.6]; n = 24; Mann-Whitney U test, P = 0.010). Fourteen daily disposable soft contact lens users and five antihistamine-releasing contact lens users eventually required anti-allergic eye drops. Kaplan-Meier analysis revealed a significant delay in the initiation of anti-allergic eye drop treatment among those using antihistamine-releasing contact lenses compared with those using daily disposable soft contact lenses (median days, daily disposable soft contact lenses: 19 days, antihistamine-releasing contact lens: 57 days; n = 24; log-rank test, P = 0.045). Conclusions: Antihistamine-releasing contact lenses can potentially mitigate worsening ocular allergic responses during the hay fever season when used appropriately as a preventive measure.

Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases.

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still's disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome.

Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease.

Human plasminogen (PLG), the zymogen of the fibrinolytic protease, plasmin, is a polymorphic protein with two widely distributed codominant alleles, PLG/Asp453 and PLG/Asn453. About 15 other missense or non-synonymous single nucleotide polymorphisms (nsSNPs) of PLG show major, yet different, relative abundances in world populations. Although the existence of these relatively abundant allelic variants is generally acknowledged, they are often overlooked or assumed to be non-pathogenic. In fact, at least half of those major variants are classified as having conflicting pathogenicity, and it is unclear if they contribute to different molecular phenotypes. From those, PLG/K19E and PLG/A601T are examples of two relatively abundant PLG variants that have been associated with PLG deficiencies (PD), but their pathogenic mechanisms are unclear. On the other hand, approximately 50 rare and ultra-rare PLG missense variants have been reported to cause PD as homozygous or compound heterozygous variants, often leading to a debilitating disease known as ligneous conjunctivitis. The true abundance of PD-associated nsSNPs is unknown since they can remain undetected in heterozygous carriers. However, PD variants may also contribute to other diseases. Recently, the ultra-rare autosomal dominant PLG/K311E has been found to be causative of hereditary angioedema (HAE) with normal C1 inhibitor. Two other rare pathogenic PLG missense variants, PLG/R153G and PLG/V709E, appear to affect platelet function and lead to HAE, respectively. Herein, PLG missense variants that are abundant and/or clinically relevant due to association with disease are examined along with their world distribution. Proposed molecular mechanisms are discussed when known or can be reasonably assumed.

Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

India's Pink-Eye Mystery: Decoding the 2023 Conjunctivitis Outbreak.

The pink eye outbreak in 2023 was caused due to humid weather conditions in most regions of India. The most affected states include Delhi, Gujrat (21% cases), Maharashtra (30%), Himachal Pradesh (4%) and Karnataka (4%). The epidemiological data indicates that males have a high prevalence rate as compared to females; urban areas were most affected, and professionals as well as students were the population group that had the highest prevalence rate. The most common clinical manifestations were the presence of red eye, eye discharge, grittiness, and eyelashes being stuck together. One of the hallmarks of histopathology is a cobblestone formation of flattened nodules with central vascular centers. Conjunctivitis is a virusmediated immune response accompanied by inflammation, which proceeds the immune reaction, giving rise to vasodilation, pseudo membrane formation, and conjunctivital discharge. The gold standard for the diagnosis of Conjunctivitis is the Adenoplus kit using PCR technology; apart from this slit lamp biomicroscope can be used for the evaluation. It is the need of the hour to spread awareness about the Pink Eye disease and the measures to prevent it.

Comparison of allergy prevalence using brinzolamide 1.0% / brimonidine 0.2% fixed combination with and without ß-blocker in glaucoma patients: a retrospective cohort study.

BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent ß-blocker. METHODS: Of these, 176 patients used a ß-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent ß-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis. RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent ß-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent ß-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent ß-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent ß-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent ß-blocker-usage group. CONCLUSIONS: Concurrent use of ß-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of ß-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

Identification of coxsackievirus A-24 GIV C5 strain as the cause of acute hemorrhagic conjunctivitis outbreak in Hyderabad, India in 2022.

Viral infection is frequently the cause for acute hemorrhagic conjunctivitis (AHC) epidemics. AHC can result from adenoviruses, with enterovirus 70 and coxsackievirus A24 being the primary agents. AHC was initially identified in Ghana in 1969, caused by enterovirus 70 and leading to a global pandemic. Since 2000, outbreaks of AHC linked to coxsackievirus A24 variant have been documented in Spain, Pakistan, Singapore, India, Korea, and China. A sudden surge of conjunctivitis cases reported in October 2022 in and out of the Hyderabad region. This infection presented with usual symptoms of redness of the eyes, discharge, pain in the eyes and crusting. Occular swab samples from 110 patients were collected in order to identify and characterize the virus that was causing the epidemic. We examined adenovirus, enterovirus, COVID-19 and Herpes Simplex Virus by using commercially kits available at the hospital. Conserved regions in the enteroviral 5'-UTR and VP2 gene were analyzed further for characterization of serotype at the National apex laboratory. None of them was found positive except Enterovirus in 16.36 % (18/110) of the patients. From enterovirus-positive samples, the coxsackievirus A24 was observed in all 18 positive samples. These clinical isolates constitute a new lineage cluster associated with genotype IV-C5, according to additional sequencing of the full-length VP2 genes and subsequent phylogenetic analysis. In conclusion, the current outbreak of acute haemorrhagic conjunctivitis in Hyderabad, India was traced to the coxsackievirus A24 strain GIV C5.

High Serum Allergen-Specific IgE of House Dust Mite in Predicting the Risk of Comorbidity in Children with Allergic Conjunctivitis.

Purpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity. Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis. Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually. Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.

Evaluation methods using tear volume in a conjunctivitis mice model.

Allergic conjunctival disease is an immune-mediated inflammatory disease of the conjunctiva. To develop clinically useful drugs, it is necessary to develop quantitative evaluation methods that reflect the clinical symptoms in experimental animal models. Allergic conjunctivitis model mice were systemically sensitised with ovalbumin (OVA) administered intraperitoneally and locally sensitised with OVA eye drops between day 14-28. Next, conjunctivitis induced by ocular administration of OVA solution to sensitised mice was evaluated based on tear volume. Additionally, we evaluated increase in tear volume induced by direct ocular instillation of histamine, compound 48/80, and carrageenan. An increase in antigen-induced tear volume was observed in the mice model. Additionally, direct instillation of histamine, compound 48/80, and carrageenan increased tear volume. Furthermore, levocabastine inhibited the increase in tear volume in antigen-induced allergic conjunctivitis and histamine- and compound 48/80-induced conjunctivitis models. In contrast, betamethasone suppressed carrageenan-induced tear volume but not histamine- or compound 48/80-induced tear volume. Histamine may be involved in increased tear volume in allergic conjunctivitis. Betamethasone is not directly involved in the action of histamine and is thought to suppress increase in tear volume. Evaluation of tear volume in a conjunctivitis mice model is highly quantitative; therefore, it is possible to evaluate drug efficacy. This is considered a useful index compared with conventional methods.

Bilateral Ophthalmomyiasis Externa of Lid by Musca domestica: A Rare Presentation.

A case of severe blepharoconjunctivitis in the last three weeks diagnosed the slit lamp as external ophthalmomyiasis. On ocular examination, numerous pupae were present on the lid margins, firmly adhering to the lid lashes bilaterally. All of them were removed mechanically under topical anesthesia. They were 67 in number. Healing occurred without any complications. In such cases of blepharoconjunctivitis, physicians should consider the possibility of ophthalmomyiasis externa, especially in places where high numbers of livestock are found. Otherwise, there is a chance of missing the diagnosis, which can be met with a more serious condition called ophthalmomyiasis interna.

Periocular fibrosarcoma with lipogranulomatous conjunctivitis in a cat.

A 9-year-old, female spayed domestic short-haired cat was presented with a 4-year history of bilateral lipogranulomatous conjunctivitis (LGC), which was confirmed via histopathology. Thirteen months following the initial biopsy, the cat was presented with a rapidly progressive mass lesion of the palpebral conjunctiva of the right eye. A surgical debulking, followed 1 month later by exenteration after marked regrowth of the mass confirmed fibrosarcoma. This case report is the first to describe a cat with chronic bilateral LGC that later developed a unilateral fibrosarcoma within the eyelid tissue of the right eye. Fibrosarcoma should be considered a differential in any cat with chronic LGC that develops a rapidly progressive mass in the eyelid.

Ocular Involvement in Patients with Brucellosis: A Single-Center Prospective Study.

PURPOSE: The aim of this study was to evaluate the prevalence, type and treatment outcomes of ocular involvement in patients with brucellosis. METHODS: This prospective, single-center study enrolled patients admitted to the infectious disease outpatient clinic with diagnosed brucellosis between July 15, 2022 and July 15, 2023. Diagnosis was based on clinical symptoms and a standard Brucella tube agglutination test (≥1/160) or a positive blood culture. Ophthalmologic examinations were performed at baseline and in the first month of treatment. Third and sixth month follow-up examinations were also performed for patients with ocular findings. RESULTS: Ocular involvement occurred in 60 (24.8%) of 242 patients. Conjunctivitis was the most common ocular involvement and was observed in 39 patients (16.1%). Uveitis was the second most common ocular involvement in 14 patients (5.8%). Scleritis was the least common ocular involvement and was observed in only one patient. Patients with ocular involvement were older (p = 0.027) and had higher rates of weight loss and spondylodiscitis (p = 0.044 and 0.001, respectively). Among laboratory parameters, erythrocyte sedimentation rate and lactate dehydrogenase levels were significantly higher in patients with ocular involvement (p = 0.001 and 0.036, respectively). There were no significant differences in other demographic, clinical, and laboratory characteristics between patients with and without ocular involvement. In 56 (93.3%) patients, the ocular findings improved during the follow-up examination. CONCLUSION: Brucellosis, a systemic infection, can manifest with ocular involvement. Early detection and treatment through ophthalmological examination are crucial in managing brucellosis.

Predisposition to conjunctivitis and male sex reduces drug survival of dupilumab in adults and adolescents.

BACKGROUND: There are currently limited data on dupilumab drug survival (DS), especially on factors possibly associated with drug discontinuation. MATERIALS AND METHODS: The primary endpoint of this study is to evaluate the parameters that may determine drug discontinuation and the predictive factors associated with dupilumab DS. We considered as independent associated factors: childhood onset of disease, gender, age of onset of AD, age of initiation of dupilumab, previous use of cyclosporine, initial mean EASI, atopic family history, and predisposition to allergic conjunctivitis. RESULTS: On 413 patients DS was 94.5% at 1 year, 89.5% at 2 years, and 83.7% at 3 years, and after a mean follow-up of 40.5 months (±1.6) 53 patients had discontinued the drug permanently (12.8%). Univariate analysis showed that the only factor associated with a reduction in drug survival was a predisposition to allergic conjunctivitis (p 0.009). At multivariate Cox regression, male sex (HR, 2.34; 95% CI, 1.14-4.78; p 0.02) and predisposition to allergic conjunctivitis (HR, 2.61; 95% CI, 1.37-5.00; p 0.004) were associated with lower DS of dupilumab. CONCLUSION: Male gender and predisposition to allergic conjunctivitis are negative predictors for maintenance of response to treatment with dupilumab and consequently associated with lower DS rates.

Mycolyltransferase is important for biofilm formation and pathogenesis of Tsukamurella keratitis.

Tsukamurella, a group of multi-drug resistant, Gram-positive, aerobic, and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of Tsukamurella keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted in vitro tests to study the pathogenesis mechanisms of Tsukamurella. There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective Tsukamurella infection. In order to look for potential candidate genes which are important in biofilm formation and Tsukamurella keratitis. We performed genome sequencing of two ocular isolates, T. pulmonis-PW1004 and T. tyrosinosolvens-PW899, to identify potential virulence factors. Through in vitro and in vivo studies, we characterized their biological roles in mediating Tsukamurella keratitis. Our findings confirmed that Tsukamurella is an ocular pathogen by fulfilling Koch's postulates, and using genome sequence data, we identified tmytC, encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing Tsukamurella keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of Tsukamurella pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for Tsukamurella infections.

A Case of Refractory Vernal Keratoconjunctivitis Showing Improvement after the Administration of Upadacitinib for the Treatment of Atopic Dermatitis.

Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab's efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis.

Allergic Conjunctivitis: Review of Current Types, Treatments, and Trends.

Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North Americans and 20% of the world's population are impacted by some form of allergy and it continues to increase in prevalence, especially among children. Specified IgE antibodies can be found in almost all cases of exposure to seasonal or perennial allergens. Activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins. The release of these factors initiates the recruitment of inflammatory cells in the conjunctival mucosa, which causes the late-phase reaction. Signs and symptoms of ocular allergies include itching, tearing, chemosis, and hyperemia, which can lead to decreased productivity and poor quality of life. Many treatment options are available to improve symptoms, including, mast cell stabilizers, antihistamines, dual-acting agents, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and other off-label treatment modalities. This review article provides an overview of different types of allergic conjunctivitis, its pathology and immunology, and recommended methods of treatment.