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1.
Curr Allergy Asthma Rep ; 24(7): 347-360, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38869807

RESUMO

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.


Assuntos
Conjuntivite Alérgica , Soluções Oftálmicas , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/imunologia , Soluções Oftálmicas/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Lágrimas
3.
JAMA Ophthalmol ; 142(7): 680-681, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38753324

RESUMO

This case report presents a case of improvement of vernal keratoconjunctivitis associated with initiation of an oral Janus kinase inhibitor upadacitinib.


Assuntos
Conjuntivite Alérgica , Compostos Heterocíclicos com 3 Anéis , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Masculino , Feminino , Criança
4.
Sci Rep ; 14(1): 9598, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671063

RESUMO

Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.6% and main commercially available eye drops. MTT assay was used to measure cell viability; oxidative stress was analyzed with a ROS-sensitive probe; and apoptosis was evaluated monitoring caspase 3/7 activation. Differences in pH value, osmolarity, viscosity and phosphate levels were identified. Among all formulations, bilastine exhibited pH, osmolarity and viscosity values closer to tear film (7.4, 300 mOsm/l and ~ 1.5-10 mPa·s, respectively), and was the only phosphates-free solution. Single-dose ketotifen did not induce ROS production, and single-dose azelastine and bilastine only induced a mild increase. Bilastine and single-dose ketotifen and azelastine showed high survival rates attributable to the absence of preservative in its formulation, not inducing caspase-3/7-mediated apoptosis after 24 h. Our findings support the use of the new bilastine 0.6% for treating patients with AC to preserve and maintain the integrity of the ocular surface.


Assuntos
Apoptose , Benzimidazóis , Caspase 3 , Sobrevivência Celular , Soluções Oftálmicas , Conservantes Farmacêuticos , Soluções Oftálmicas/farmacologia , Humanos , Conservantes Farmacêuticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Benzimidazóis/farmacologia , Benzimidazóis/química , Caspase 3/metabolismo , Apoptose/efeitos dos fármacos , Piperidinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Caspase 7/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/patologia , Conjuntivite Alérgica/metabolismo , Ftalazinas/farmacologia , Concentração Osmolar , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Células Cultivadas , Viscosidade
5.
Indian J Ophthalmol ; 72(7): 1007-1011, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454855

RESUMO

PURPOSE: To elucidate the efficacy and safety profile of interferon α-2b in vernal keratoconjunctivitis (VKC). METHODS: In this prospective interventional study, VKC patients fulfilling the inclusion and exclusion criteria were included and their signs and symptoms were scored based on the Clinical Scoring System. Patients were treated with topical interferon α-2b eye drop (1 MIU/ml) QID dosing for 6 weeks. Changes in symptoms and signs were evaluated at 2, 4, 8 weeks and 6 months after initiating treatment. A higher score meant severe disease, and a decline in score meant improvement in clinical signs and symptoms. Categorical variables were presented in number and percentage (%) and continuous variables as mean ± standard deviation (SD). Post-medication total subjective symptom score (TSSS) and total objective sign score (TOSS) were compared with baseline, and a P- value of <0.05 was considered significant. Possible ocular and systemic complications were evaluated. RESULTS: The study included 40 patients (32 male and eight female) with a mean age of 8.05 ± 2.33 years. Mean baseline TSSS and TOSS were 6.71 ± 0.564 and 6.59 ± 0.262, respectively, which reduced to 2.71 ± 0.011 ( P = 0.040) and 2.96 ± 0.210 ( P = 0.032), respectively, at 4 weeks and further reduced to 0.42 ± 0.552 and 0.47 ± 0.434, respectively, at 8 weeks. After 6 months of stopping the drug, mean TSSS and TOSS did increase to 2.80 ± 0.820 ( P = 0.044) and 2.50 ± 0.520 ( P = 0.030), respectively, but was still statistically significant improvement compared to the baseline. Also, no ocular or systemic side effects were observed anytime during the study period. CONCLUSION: Eye drop interferon α-2b (1 million IU/ml) is a safe and effective option as first-line monotherapy for VKC. No side effects and recurrence were observed for 6 months.


Assuntos
Conjuntivite Alérgica , Interferon alfa-2 , Soluções Oftálmicas , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Masculino , Feminino , Estudos Prospectivos , Interferon alfa-2/administração & dosagem , Criança , Resultado do Tratamento , Seguimentos , Relação Dose-Resposta a Droga , Adolescente , Administração Tópica , Pré-Escolar , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos
6.
J Sci Food Agric ; 104(10): 5846-5859, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38385802

RESUMO

BACKGROUND: Allergic conjunctivitis is one of the most common eye disorders. Different drugs are used for its treatment. Hesperidin is an active substance isolated from Citrus sinensis L. (Rutaceae) fruit peels, with known anti-inflammatory activity but low solubility. It was complexed with cyclodextrin and encapsulated in situ gel to extend its duration in the eye. RESULTS: The optimized formulation comprised 1% hesperidin, 1.5% hydroxyethyl cellulose, and 16% poloxamer 407. The viscosity at 25 °C was 492 ± 82 cP, and at 35 °C it was 8875 ± 248 cP, the pH was 7.01 ± 0.03, gelation temperature was 34 ± 1.3 °C, and gelation time was 33 ± 1.2 s. There was a 66% in vitro release in the initial 2 h, with a burst effect. A lipoxygenase (LOX) inhibition test determined that hesperidin was active at high doses on leukotyrens seen in the body in allergic diseases. In cell-culture studies, the hesperidin cyclodextrin complex loaded in situ gel, BRN9-CD (poloxamer 16%, hydroxy ethyl cellulose (HEC) 1.5%), enhanced cell viability in comparison with the hesperidin solution. It was determined that BRN9-CD did not cause any irritation in the ocular tissues in the Draize test. CONCLUSION: The findings of this study demonstrate the potential of the in situ gel formulation of hesperidin in terms of ease of application and residence time on the ocular surface. Due to its notable LOX inhibition activity and positive outcomes in the in vivo Draize test, it appears promising for incorporation into pharmaceutical formulations. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Sistemas de Liberação de Medicamentos , Géis , Hesperidina , Hesperidina/química , Hesperidina/farmacologia , Hesperidina/análogos & derivados , Géis/química , Animais , Humanos , Citrus sinensis/química , Conjuntivite Alérgica/tratamento farmacológico , Composição de Medicamentos , Viscosidade , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica
7.
Ophthalmologie ; 121(3): 180-186, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-38363381

RESUMO

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 T­helper 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.


Assuntos
Conjuntivite Alérgica , Criança , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Ciclosporina , Tacrolimo , Fatores Imunológicos/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Soluções Oftálmicas/uso terapêutico
8.
Eye (Lond) ; 38(5): 937-944, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37904000

RESUMO

PURPOSE: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). METHODS: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. RESULTS: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. CONCLUSIONS: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.


Assuntos
Conjuntivite Alérgica , Síndromes do Olho Seco , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Ciclosporina/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Cloridrato de Olopatadina/uso terapêutico , Quimiocina CCL26 , Metaloproteinase 9 da Matriz/uso terapêutico , Lubrificantes Oftálmicos/uso terapêutico , Interleucina-6 , Estudos Prospectivos , Síndromes do Olho Seco/tratamento farmacológico , Citocinas/metabolismo , Prurido/tratamento farmacológico , Imunoglobulina E/uso terapêutico , Lágrimas/metabolismo
9.
Surv Ophthalmol ; 69(2): 265-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37890678

RESUMO

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients' quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.


Assuntos
Conjuntivite Alérgica , Criança , Humanos , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/epidemiologia , Ciclosporina/uso terapêutico , Qualidade de Vida , Túnica Conjuntiva/patologia , Soluções Oftálmicas/uso terapêutico
10.
Cornea ; 43(2): 228-232, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747690

RESUMO

PURPOSE: The aim of this study was to demonstrate the efficacy of cyclosporine A 0.1% cationic emulsion (CsA CE) eye drops 4 times a day in pediatric patients affected by a moderate form of vernal keratoconjunctivitis (VKC). METHODS: This was a prospective study of pediatric patients, aged 5-16 years, with an active moderate form of VKC who were poor responders to topical antihistamines treatment and were treated 4 times a day with CsA CE. The clinical signs were graded for analysis as follows: hyperemia, tarsal papillae, and limbal papillae. RESULTS: Twenty-eight patients (22 males and 6 females) with a minimum follow-up period of 3 months were included in the analysis. Statistical analysis excluded tarsal papillae because of the very low baseline value. The clinical score of hyperemia and limbal papillae improved from the first evaluation and was maintained over the follow-up. No side effects were noted. CONCLUSION: CsA CE has been proposed as a treatment for severe forms of VKC. This study has shown that administration 4 times a day is also effective in the treatment of moderate forms of VKC in children.


Assuntos
Conjuntivite Alérgica , Hiperemia , Masculino , Feminino , Humanos , Criança , Ciclosporina , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Imunossupressores , Estudos Prospectivos , Emulsões/uso terapêutico , Hiperemia/induzido quimicamente , Hiperemia/tratamento farmacológico , Soluções Oftálmicas
11.
J Ocul Pharmacol Ther ; 40(3): 173-180, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38150534

RESUMO

Purpose: To investigate the in vivo efficacy of epinastine cream in type I allergic models. Methods: The dose, timing, and antiallergic effect of epinastine cream on the conjunctiva were evaluated postapplication to the eyelid skin of guinea pigs with histamine- or ovalbumin-induced allergic conjunctivitis. Additionally, we assessed its antiallergic effects on the skin postapplication to the dorsal skin of guinea pigs with ovalbumin-induced passive cutaneous anaphylaxis. Efficacy was estimated by determining the amount of dye that leaked from conjunctival or dorsal skin tissue vessels as a measure of vascular permeability, scoring the severity of allergic symptoms, and observing the scratching behaviors using clinical parameters. Results: In the histamine-induced conjunctivitis model, epinastine cream strongly inhibited conjunctival vascular permeability in a dose-dependent manner. The inhibitory effect of 0.5% epinastine cream 24 h postapplication was significantly higher than that of 0.1% epinastine hydrochloride ophthalmic solution 8 h postadministration. Additionally, the 0.5% epinastine cream inhibited conjunctival vascular permeability 15 min postapplication, and the effect was sustained over 24 h. Furthermore, the 0.5% epinastine cream effectively suppressed clinical symptom scores and exhibited ameliorated scratching bouts in conjunctival allergic reactions in the experimental allergic conjunctivitis model. Additionally, it significantly inhibited vascular permeability in skin allergic reactions in the passive cutaneous anaphylaxis model. Conclusions: The results suggest that epinastine cream is a strong, long-lasting, and skin-penetrating inhibitor of type I allergic reactions. The 0.5% epinastine cream applied once daily could be a promising, potent, and long-acting therapeutic agent for allergic conjunctivitis.


Assuntos
Antialérgicos , Conjuntivite Alérgica , Dibenzazepinas , Imidazóis , Animais , Cobaias , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/diagnóstico , Histamina/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Ovalbumina/efeitos adversos , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico
13.
J Investig Allergol Clin Immunol ; 33(6): 431-438, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38095492

RESUMO

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.


Assuntos
Conjuntivite Alérgica , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Soluções Oftálmicas/uso terapêutico
14.
J Investig Allergol Clin Immunol ; 33(6): 439-445, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38095493

RESUMO

Tear dysfunction syndrome, also known as dry eye disease (DED), is a multifactorial disease of the ocular surface characterized by the loss of tear film homeostasis. DED shows a significant clinical overlap with ocular allergy (OA), which alters tear film homeostasis, thus predisposing the patient to DED. Both conditions constitute the most common ocular surface disorders and have a potentially severe impact on patients' quality of life. Clinical practice guidelines recommend topical therapies as first-line treatment for OA. However, eye drop formulations may contain additional substances that can contribute to ocular surface damage and the development of DED. Therefore, physicians treating ocular allergy should be aware of problems affecting the tear film, the role of tear film disruption in OA, and topical treatment to prevent or minimize DED. The aim of this review is to present an updated overview of the topic.


Assuntos
Conjuntivite Alérgica , Síndromes do Olho Seco , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Qualidade de Vida , Síndromes do Olho Seco/tratamento farmacológico , Lágrimas , Soluções Oftálmicas
15.
Orv Hetil ; 164(43): 1686-1692, 2023 Oct 29.
Artigo em Húngaro | MEDLINE | ID: mdl-37898906

RESUMO

Allergic and immunopathological diseases of the ocular surface are inflammations that can occur with mild to severe symptoms that cause visual impairment. Allergic inflammations mainly affect the conjunctiva, causing acute and/or chronic conjunctivitis. Several forms are distinguished: seasonal allergic conjunctivitis, vernal conjunctivitis, atopic keratoconjunctivitis, contact allergy, giant papillary conjunctivitis. The most common is the seasonal form, which is linked to seasons. Allergic ocular surface processes require local treatment with artificial tears, anti-allergic eye drops. If complications occur, topical corticosteroid and cyclosporin treatment may be used. Immunopathological inflammations of the ocular surface are associated with systemic diseases. Keratoconjunctivitis sicca, although occurring in the absence of systemic disease, is a common companion of Sjögren's syndrome and collagen diseases. Ocular pemphigoid belongs to the group of mucous membrane pemphigoids. After the initial conjunctivitis symptoms, subconjunctival fibrosis begins, leading to the development of sym- and ankyloblepharon. In the final stage, the ocular surface is covered by scar tissue (ocular cicatricial pemphigoid) which practically results in loss of vision. Peripheral ulcerative keratitis is usually associated with collagen vascular disease, rheumatoid arthritis. A 3-4 mm long, curved infiltration starting near the limbus becomes ulcerated and then perforates, on which the iris may prolapse. First, systemic treatment is required, which is an interdisciplinary task. Topical corticosteroid and cyclosporine eye drops may be administered. In the case of corneal perforation, amniotic membrane transplantation and/or keratoplasty may be performed. Orv Hetil. 2023; 164(43): 1686-1692.


Assuntos
Conjuntivite Alérgica , Conjuntivite , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Glucocorticoides , Inflamação , Soluções Oftálmicas
16.
Sci Rep ; 13(1): 18143, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875539

RESUMO

Ophthalmic preparations that contain ketorolac tromethamine (KET) and olopatadine HCl (OLO) are used to relieve seasonal allergies and allergic conjunctivitis. Simultaneous quantification of KET and OLO was held by validated and simple spectrophotometric methods. KET was determined directly from the fundamental UV absorption spectra (at 323 nm), while OLO was determined after performing either dual wavelength or ratio derivative methods. The first method was based on measuring the absorbance difference (ΔA) between 243 and 291 nm, while the second depended on generating first derivative ratio spectra using 3.0 µg/mL KET as a divisor and measuring OLO responses at 234 nm (minima). Multiple standard addition method was applied to enable the determination of OLO which is considered as the weakly absorbing species as well as the minor component in a challenging dosage form ratio (4:1). The linearity ranges of the developed methods were 3-12 µg/mL and 4-40 µg/mL for KET and OLO, respectively. Simultaneous determination of both drugs was successfully implemented to lab prepared eye drops that contain KET, OLO and benzalkonium chloride as an inactive ingredient. Greenness assessment indicates minimal impact on environment. The developed methods determined the cited drugs with % recovery ± SD of 99.63 ± 0.01 for KET, 100.90 ± 0.02 and 100.31 ± 0.01 for OLO using dual wavelength and first derivative ratio methods, respectively. Using F-test and t-test at confidence level %95 to compare between the results of the presented methods and a reported method show no significant difference which allows precise, accurate, rapid, and simple quantification of quality control samples that contain KET and OLO.


Assuntos
Conjuntivite Alérgica , Cetorolaco de Trometamina , Humanos , Cloridrato de Olopatadina , Soluções Oftálmicas , Conjuntivite Alérgica/tratamento farmacológico , Espectrofotometria
17.
Stem Cell Res Ther ; 14(1): 281, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37784129

RESUMO

BACKGROUND: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC). METHODS: A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells. RESULTS: Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice. CONCLUSIONS: Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.


Assuntos
Conjuntivite Alérgica , Células-Tronco Mesenquimais , Humanos , Animais , Camundongos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/patologia , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical
18.
Clin Ther ; 45(12): 1284-1288, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37872059

RESUMO

PURPOSE: This study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC). METHODS: This Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale. FINDINGS: All groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable. IMPLICATIONS: Although treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). CLINICALTRIALS: gov identifier: NCT00328653.


Assuntos
Conjuntivite Alérgica , Ciclosporina , Ceratite , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Ciclosporina/uso terapêutico , Método Duplo-Cego , Emulsões/uso terapêutico , Ceratite/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Prurido , Resultado do Tratamento
19.
JCI Insight ; 8(21)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37819721

RESUMO

The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest symptoms within minutes after pollen exposure, the mechanisms of the rapid transport of the allergens remain unclear. In the present study, we found that the instillation of pollen shells rapidly induces a large number of goblet cell-associated antigen passages (GAPs) in the conjunctiva. Antigen acquisition by stromal cells, including macrophages and CD11b+ dendritic cells, correlated with surface GAP formation. Furthermore, a substantial amount of antigen was transported to the stroma during the first 10 minutes of pollen exposure, which was sufficient for the full induction of an allergic conjunctivitis mouse model. This inducible, rapid GAP formation and antigen acquisition were suppressed by topical lidocaine or trigeminal nerve ablation, indicating that the sensory nervous system plays an essential role. Interestingly, pollen shell-stimulated GAP formation was not suppressed by topical atropine, suggesting that the conjunctival GAPs and intestinal GAPs are differentially regulated. These results identify pollen shell-induced GAP as a therapeutic target for allergic conjunctivitis.


Assuntos
Conjuntivite Alérgica , Animais , Camundongos , Humanos , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/tratamento farmacológico , Células Caliciformes , Alérgenos , Pólen , Túnica Conjuntiva
20.
Clin Rev Allergy Immunol ; 65(2): 277-329, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37658939

RESUMO

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.


Assuntos
Conjuntivite Alérgica , Humanos , Conjuntivite Alérgica/terapia , Conjuntivite Alérgica/tratamento farmacológico , Úlcera/tratamento farmacológico , Ciclosporina/uso terapêutico , Tacrolimo/uso terapêutico , Soluções Oftálmicas/uso terapêutico
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