Allergic Conjunctivitis Management: Update on Ophthalmic Solutions

The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Dry eye disease (DED) is a clinically significant multifactorial disorder of the ocular surface and tear film as it results in ocular discomfort and visual impairment and predisposes the cornea to infections. It is important for the quality of life and tends to be a chronic disease. It is also common, as the prevalence is estimated between 5 % to 30 % and this increases with age. Therefore, it is recognised as a growing public health problem that requires correct diagnosis and appropriate treatment. There are two main categories of DED: the deficiency of tear production (hyposecretive), which includes Sjögren syndrome, idiopathic or secondary to connective tissue diseases (e.g. rheumatoid arthritis), and non-Sjögren syndrome (e.g. age-related); and the tear evaporation category, where tears evaporate from the ocular surface too rapidly due to intrinsic causes (e.g. meibomian gland disease or eyelid aperture disorders) or extrinsic causes (e.g. vitamin A deficiency, contact lenses wear, ocular allergies). Management of the disease aims to enhance the corneal healing and reduce patient’s discomfort. This is based on improving the balance of tear production and evaporation by increasing the tear film volume (lubrication drops) and improving quality of tear film (ex omega-3 supplements, lid hygiene, tetracyclines), reducing the tear film evaporation (paraffin ointments, therapeutic contact lenses), reducing tear’s drainage (punctal plugs, cautery) and finally by settling down the ocular surface inflammation (steroids, cyclosporine, autologous serous), as appropriate. In this article we will review the clinical presentation, differential diagnosis and treatment options for DED.

Background The pathogenesis of allergic conjunctivitis has not been clearly established.Current researchers indicate that interleukin-4 (IL-4), IL-5 and IL-13 may play an important role in allergic conjunctivitis.But whether the roles of these inflammatory factors are same in different types of allergic conjunctivitis remains unclear. Objective This study was to investigate the expressions of IL-4, IL-5 and IL-13 in ocular surface with different types of allergic conjunctivitis. Methods A prospective cohort study was designed.Eighty individuals were recruited in Shanxi Eye Hospital from April 2013 to September 2014, including 20 patients with vernal keratoconjunctivitis (VKC), 20 patients with seasonal allergic conjunctivitis (SAC), 20 patients with perennial allergic conjunctivitis (PAC) and 20 normal healthy subjects.Surficial tissues were binocularly scraped using disinfected scraper from upper eyelid conjunctiva, and 4 μl of tear fluid was obtained with capillary tube.The expressions of IL-4, IL-5 and IL-13 protein and mRNA in the conjunctival epithelial cells were detected by immunohistochemistry and real-time fluorescence quantitative PCR.The IL-4, IL-5 and IL-13 concentrations in tear fluid were assayed by Luminex method.This study complied with Declaration of Helsinki and the research protocol was approved by the Shanxi Eye Hospital Ethics Committee.Written informed consent was obtained from each subject prior to entering the cohort. Results IL-4, IL-5 and IL-13 were positively expressed in cytoplasm of conjunctival epithelial cells in the VKC group, SAC group and PAC group, but the expressions of IL-4, IL-5 and IL-13 were absent in the normal control group.The relative expression levels of IL-4 mRNA were 4.11±1.24, 2.71±0.71 and 2.00±0.80; the relative expression levels of IL-5 mRNA were 4.02±0.43, 2.07±0.45 and 1.47±0.50; and the relative expression levels of IL-13 mRNA expression levels were 6.44±0.66, 4.35±1.26 and 2.39±0.86 in the VKC group, SAC group and PAC group, showing significant differences among the 4 groups (F=51.32, 220.18, 162.49, all at P<0.01). The relative expression levels of IL-4, IL-5 and IL-13 mRNA were significantly higher in the VKC group than those in the SAC group and PAC group; and those in the SAC group were significantly elevated in comparison with the PAC group (all at P<0.05). No IL-4, IL-5 and IL-13 were detected in the tear fluid in the normal control group; while the concentrations of IL-4, IL-5 and IL-13 in the tear fluid were (14.06±3.50), (10.88±1.82) and (34.28±8.42) pg/ml in the VKC group, and (7.71±0.65), (5.10±1.33), (23.77±6.29) pg/ml in the SAC group as well as (3.30±1.50) pg/ml, (2.43±1.28) pg/ml and (17.67±4.28) pg/ml in the PAC group, showing significant differences among the 3 groups (F=200.29, 260.49, 128.23, all at P<0.01). IL-4, IL-5 and IL-13 concentrations in the tear fluid were significantly higher in the VKC group than those in the SAC group and PAC group, and those in the SAC group were significantly raised in comparison with the PAC group (all at P<0.01). Conclusions IL-4, IL-5 and IL-13 participate in the pathogenesis of multiple allergic conjunctivitis, but their expressions in the ocular surficial tissue are discriminatory in different types of allergic conjunctivitis. Key words: Conjunctivitis, allergic/immunology; T-lymphocytes; Inflammatory, ocular/immunology; Interleukin-4; Interleukin-5; Interleukin-13; Humans; Epithelium, eye; Tear

Seeing through tears: Understanding and managing dry eye disease.

To provide an overview of the pathogenic mechanisms underlying the correlation between ocular allergy and dry eye disease (DED), highlighting how the first condition may be a risk factor for the second one. Recent advances in our comprehension of the pathogenesis of ocular allergy and DED allow identifying several pathways of interaction between these two conditions. A growing body of evidence supports the role of ocular allergy as a risk factor for DED. Ocular allergy, particularly the severe forms of keratoconjunctivitis, can impact on different key mechanisms of the DED vicious cycle, including tear film instability, ocular surface inflammation and damage, and neurosensory abnormalities. Ocular allergy and DED are two common, relevant, symptomatic, not mutually exclusive conditions affecting the ocular surface. They share some clinical and biochemical features. To better understand the complex interactions between these two conditions, it's essential to consider the very wide spectrum of clinical conditions included in the term ocular allergy and the still largely unexplored peculiarities of the pediatric ocular surface physio-pathology and DED.

Purpose The aim of this study was to investigate the correlation and validity of tear film allergen-specific immunoglobulin E (IgE) in relation to the skin prick test in diagnosing different types of allergic conjunctivitis. Design The study design was a prospective randomized case series. Patients and methods One hundred and twenty patients with allergic conjunctivitis were included in this study and were classified into four groups according to the type of allergy. Group 1 included 48 patients with perennial allergic conjunctivitis. Group 2 included 35 patients with seasonal allergic conjunctivitis. Group 3 included 30 patients with vernal keratoconjunctivitis (VKC), and group 4 included seven patients with atopic keratoconjunctivitis. All patients were subjected to the skin prick test, which was performed with aeroallergen panel using kits containing different inhalant allergens, positive control (histamine 1 mg/ml), and negative control (saline 0.9%). Tear samples were collected using the microcapillary method for the quantitative determination of specific IgE using immune blot assay. Data were evaluated and statistically analyzed. Results In this study, the skin prick test and specific IgE were performed to 11 different allergens and the results revealed that the most common mixed allergens were mixed pollen, mixed mould, and mixed mite. Validity of tear film-specific IgE in the detection of allergens was assessed against the skin prick test (gold standard). There was IgE specificity of 100%, whereas the sensitivity ranged from 50 to 100% to the three common allergens in the four groups. There was a statistically significant correlation between specific IgE and the skin prick test for the most common allergens in patients with perennial allergic conjunctivitis, seasonal allergic conjunctivitis, and VKC (except for mould allergens in the VKC group). There was only a statistically significant correlation between specific IgE and the skin prick test for mite allergen in patients with atopic keratoconjunctivitis. Conclusion Tear film-specific IgE has a statistically significant correlation and validity when compared with the skin prick test in diagnosing the causative allergen in different types of allergic conjunctivitis. It could be a good alternative to the skin prick test in the diagnosis of allergic conjunctivitis with high sensitivity and specificity and fewer complications and limitations.

Allergic diseases have greatly increased in industrialized countries. About 30% of people suffer from allergic symptoms and 40%–80% of them have symptoms in the eyes. Atopic conjunctivitis can be divided into seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). The treatment of SAC is simple; antihistamines, anti-inflammatory agents, or chromoglycate. In severe cases of SAC, subcutaneous or sublingual immunotherapy is helpful. PAC needs longer therapy, often year round, with mast cell stabilizers, antihistamines, and sometimes local steroids. Atopic keratoconjunctivitis is a more severe disease showing chronic blepharitis often connected with severe keratitis. It needs, in many cases, continuous treatment of the lid eczema and keratoconjunctivitis. Blepharitis is treated with tacrolimus or pimecrolimus ointment. Conjunctivitis additionally needs corticosteroids and, if needed, cyclosporine A (CsA) drops are administered for longer periods. Basic conjunctival treatment is with mast cell-stabilizing agents and in addition, antihistamines are administered. Vernal keratoconjunctivitis is another chronic and serious allergic disease that mainly affects children and young people. It is a long-lasting disease which commonly subsides in puberty. It demands intensive therapy often for many years to avoid serious complicating corneal ulcers. Treatment is mast cell-stabilizing drops and additionally antihistamines. In relapses, corticosteroids are needed. When the use of corticosteroids is continuous, CsA drops should be used, and in relapses, corticosteroids should be used additionally. Nonallergic eosinophilic conjunctivitis (NAEC) is a less known, but rather common, ocular disease. It affects mostly middle-aged and older women. The eye symptoms of NAEC are largely similar to those seen in chronic allergic conjunctivitis. Basic therapy is mast cell-stabilizing drops. Eosinophilic inflammation needs additional corticosteroids. In severe cases, CsA drops are recommended. Antihistamines should be avoided. It is important to recognize the different forms of allergic ocular diseases and to start the treatment early and intensively enough to avoid chronicity of the disease and accompanying tissue destruction.

ABSTRACTPurpose: Olopatadine hydrochloride 0.2% (Pataday, Alcon, Fort Worth, USA) is a topical ocular anti-allergic agent that has shown high rates of efficacy in treating ocular itching, the primary symptom of allergic conjunctivitis, and allows for once-daily dosing. Since some patients suffer from signs or symptoms of dry eye in addition to ocular allergy, this study was designed to evaluate the safety of olopatadine 0.2% in a population of patients with both allergic conjunctivitis and dry eye.Methods: This was a single-center, 3-visit, double-masked, randomized study. Fifty-two patients diagnosed with ocular allergy and mild-to-moderate dry eye were evaluated. After a run-in period, patients were randomized to receive either olopatadine hydrochloride 0.2% or a tear saline, and self-dosed once-daily for 1 week. Outcome measures included tear film break-up time, corneal and conjunctival staining, tear volume and flow as measured by fluorophotometry, Schirmer's test, injection, and symptom evaluations.Results: No significant differences between the treatment groups were observed ( p > 0.05). No serious adverse events occurred during the trial. Variability in the presentation of dry eye can hinder the observation of treatment effects. Although the study design facilitated the comparison of olopatadine 0.2% against an agent that was certain to not exacerbate dry eye, future comparison of olopatadine 0.2% against other agents in its drug class would provide useful information about relative drug tolerabilities.Conclusion: As there were no significant changes in the signs and symptoms of dry eye, olopatadine hydrochloride 0.2% is safe to use in ocular allergy patients with mild-to-moderate dry eye.

Purpose to evaluate in a retrospective study ocular surface impairment and tear osmolarity in children presenting ongoing ocular allergy. Tears are necessary for continued health of ocular surface and tear osmolarity is considered a key point for tear film impairment and ocular surface damage.Methods Our retrospective study included 20 children (mean age 11 yo, range 6 to 17 yo) of two groups that presented at ocular consultation of our hospital. Group a, 10 children with ongoing ocular allergy, group b 10 control children who had been tested but finally did not present any sign of allergy or dry eye. All the children underwent a tear osmolarity measure prior to complete ocular consultation to be aware of influencing results by the examination. The tear osmolarity measure was obtained with the Tear Lab Osmolarity System (OcuSense). A complete ocular examination was also performed. So the type of ocular allergy was diagnosed.Results In group a, all the children presented clinical signs of on going ocular allergy with conjunctival redness, follicles and/or papillae. In two cases severe keratitis was present. In group b no ocular signs of conjunctiva anomalies were found. Mean tear osmolarity in group b, was 305mOsm/l and in group a, was 316mOsm/l. Tear osmolarity appeared higher in the ocular allergy group than in the non symptomatic children. Younger children had a higher measure of tear osmolarity.Conclusion In adults 305mOsm/l is a cut‐off value for dry eye. In our study this measure appears similar to adults but could be higher in youngest children. In children with ocular allergy, higher measure of tear osmolarity indicates an ocular surface damage that is underestimated. Tear osmolarity can be useful to manage ocular surface disease in children.

Dry eye disease (DED) is an ocular condition characterized by altered tear film homeostasis, resulting in symptoms like tear film instability, hyperosmolarity, inflammation, and neurosensory abnormalities. It affects visual acuity and quality of life and is influenced by age, gender, and environmental factors. The first line of treatment consists of dynamically developing artificial tears, gels, and eyelid sprays, which can be supplemented with natural ingredients for enhanced efficacy. Other therapeutic steps include auto-logous serum tears, anti-inflammatory and immunosuppressive eyedrops, or oral tablets. Management also targets Meibomian gland dysfunction and the ocular surface micro-biome. This article explores various therapeutic approaches, including natural compounds and complementary strategies. Natural compounds, such as vitamins, and herbal substances (e.g., trehalose), offer promising benefits in enhancing tear film stability and ocular surface protection. Apitherapeutic products like manuka honey and propolis exhibit antibacterial and anti-inflammatory properties. Additionally, human tissue-derived solutions, such as auto-logous serum tears and amniotic membrane extracts, hold the potential for ocular surface regeneration. Other strategies, including polyherbal eye drops, liposomal eyelid sprays, and microbiome-supporting solutions offer alternative therapeutic avenues. Moreover, patient education, lifestyle modifications, and interdisciplinary collaboration play crucial roles in DED management, emphasizing the importance of holistic care approaches.

The most common disorders of the ocular surface are dry eye disease (DED) and ocular allergy (OA). These conditions are frequently coexisting with or without a clinical overlap and can cause a severe impact on the patient's quality of life. Therefore, it can sometimes be hard to distinguish between DED and OA because similar changes and manifestations may be present. Atopic patients can also develop DED, which can aggravate their manifestations. Moreover, patients with DED can develop ocular allergies, so these two pathological entities of the ocular surface can be considered as mutual conditions that share the same background. Nowadays, by using different techniques to collect tissue from ocular surfaces, the changes in molecular homeostasis can be detected and this can lead to a precise diagnosis. The article provides an up-to-date review of the various ocular surface biomarkers that have been identified in DED, OA, or both conditions. Abbreviations: DED = dry eye disease, OA = ocular allergy, SS = Sjogren syndrome, TBUT = tear break up time, TFO = tear film osmolarity, AKC = Atopic keratoconjunctivitis, ANXA1 = Annexin 1, ANXA11 = Annexin 11, CALT = Conjunctival associated lymphoid tissue, CCL2/MIP-1 = Chemokine (C-C motif) ligand2/Monocyte chemoattractant protein 1, CCL3/MIP-1α = Chemokine (C-C motif) ligand 3/Macrophage inflammatory protein 1 alpha, CCL4/MIP-1β = Chemokine (C-C motif) ligand 4/Macrophage inflammatory protein 1 beta, CCL5/RANTES = Chemokine (C-C motif) ligand 5 /Regulated on Activation, Normal T cell Expressed and Secreted, CCR2 = Chemokine (C-C motif) receptor 2, CCR5 = Chemokine (C-C motif) receptor 5, CD3+ = Cluster of differentiation 3 positive, CD4+ = Cluster of differentiation 4 positive, CD8+ = Cluster of differentiation 8 positive, CGRP = Calcitonin-gene-related peptide, CX3CL1 C-X3 = C motif -chemokine ligand 1 /Fractalkine, CXCL8 = Chemokine (C-X-C motif) ligand 8, CXCL9 = Chemokine (C-X-C motif) ligand 9, CXCL10 = Chemokine (C-X-C motif) ligand 10, CXCL11 = Chemokine (C-X-C motif) ligand 11, CXCL12 = Chemokine (C-X-C motif) ligand 12, CXCR4 = Chemokine (C-X-C motif) receptor 4, EGF = Epidermal growth factor, HLA-DR = Human leukocyte antigen-D-related, ICAM-1 = Intercellular adhesion molecule 1, IFN-γ = Interferon-gamma, IgG = Immunoglobulin G, IgE = Immunoglobulin E, IL-1 = Interleukin-1, IL-1α = Interleukin-1 alpha, IL-1β = Interleukin-1 beta, CGRP = Calcitonin-Gene-Related Peptide, IL-3 = Interleukin-3, IL-4 = Interleukin-4, IL-6 = Interleukin-6, IL-8 = Interleukin-8, IL-10 = Interleukin-10, IL-17 = Interleukin-17, IL-17A = Interleukin-17A, LPRR3 = Lacrimal proline-rich protein 3, LPRR4 = Lacrimal proline-rich protein 4, MUC5AC = Mucin 5 subtype AC, oligomeric mucus/gel-forming, MUC16 = Mucin 16, OCT = Optical coherence tomography, OGVHD = Ocular graft versus host disease, PAX6 = Paired-box protein 6, VKC = Vernal keratoconjunctivitis, TGF-β = Transforming growth factor β, S100 = proteins Calcium activated signaling proteins, Th1 = T helper 1 cell, Th17 = T helper 17 cell, MGD = Meibomian gland dysfunction, TFOS = Tear film and ocular surface society, SS-KCS = Keratoconjunctivitis Sicca, MMP-9 = Matrix metalloproteinase 9, MMP-1 = Matrix metalloproteinase 1, ZAG = Zinc alpha glycoprotein, CBA = Cytometric bead array, MALDI TOF-MS = matrix assisted laser desorption ionization-time of flight, SELDI TOF-MS = surface-enhanced laser desorption ionization-time of flight, IVCM = in vivo confocal microscopy, AS-OCT = anterior segment optical coherence tomography, iTRAQ = Isobaric tags for relative and absolute quantitation, LC-MS = Liquid chromatography-mass spectrometry, LCN-1 = lipocalin 1, PIP = prolactin induced protein, NGF = Nerve growth factor, PRR4 = proline rich protein 4, VIP = Vasoactive intestinal peptide, ELISA = enzyme linked immunoassay, TNF-α = tumor necrosis factor alpha, PAC = perennial allergic conjunctivitis, SAC = seasonal allergic conjunctivitis, IC = impression cytology, RT-PCR = reverse transcription polymerase chain reaction, PCR = polymerase chain reaction, APCs = antigen-presenting cells, NK cells = natural killer cells, HEL = hexanoyl-lysine, 4-HNE = 4-hydroxy-2-nonenal, MDA = malondialdehyde.

A standard approach to the diagnosis of dry eye disease across eye care practitioners is critical to reassuring the patient, providing consistency between practitioners and informing governments as to the true prevalence and resulting healthcare needs. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III has reviewed the evidence-base since their previous reports published in 2017 and revised the definition to "Dry eye is a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and/or ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities are etiological factors." Key features from the definition include that dry eye disease is multifactorial, is a disease and not a syndrome and is always symptomatic. Differential diagnosis and ocular examination guidance is given along with the risk factors that should be discussed with the patient. The recommended screening questionnaire is the OSDI-6 with a cut-off score ≥4. A positive result together with a non-invasive breakup time <10s or alternatively tear film hyperosmolarity (≥308mOsm/L in either eye or an interocular difference >8mOsm/L) or alternatively >5 corneal fluorescein and/or >9 conjunctival lissamine green punctate spots and/or lid margin lissamine green staining of ≥2mm length & ≥25 % width, gives a diagnosis of dry eye. Subclassification was separated into tear film deficiencies (lipid, aqueous and mucin/glycocalyx), eyelid anomalies (blink/lid closure and lid margin) and ocular surface abnormalities (anatomical misalignment, neural dysfunction, ocular surface cell damage/disruption and primary inflammation/oxidative stress) components, with appropriate clinical tests and cut-offs provided to identify these etiological drivers in an individual, to inform appropriate management and therapy.

Seasonsal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) as well as intermittent and persistent allergic rhinitis are widespread diseases. Because a combined occurrence of ocular and nasal symptoms is very common the summarising term allergic rhinoconjunctivitis is frequently used. SAC and PAC representing the two acute forms of allergic conjunctivitis account for more than 90% of all cases of allergic conjunctivitis. Compared to the chronic forms of allergic conjunctivitis their course of disease is milder. Nevertheless because of their high prevalence and the proven influence on patients' quality of life they possess clinical and socioeconomic relevance. Allergic rhinoconjunctivitis is caused by a type 1 IgE-mediated hypersensitivitity reaction that is provoked by aeroallergens in the majority of cases. The pathognomonic sign is itching. Besides, typical ocular findings are chemosis, conjunctival injection,watery secretion and lid swelling. Otorhinolaryngologists' findings include rhinorrhea, postnasal drip and sneezing. Problems in breathing through the nose resulting from nasal obstruction can cause impaired nighttime sleep and daytime somnolence. In addition to a reduction of allergen exposure by modification of environment and life style factors, in mild forms of SAC and PAC artificial tears are recommended. Topical antihistamines can generate rapid relief from acute symptoms and itching. Topical mast cell stabilisers however provide long-term effects. Dual action drugs that combine antihistamines and mast cell stabilisers show increased patient compliance due to reduced application frequency. Use of topical steroids should be cautious and only temporary. For prolonged treatment periods unpreserved anti-allergic eye-drops should be preferred. Combined topical antihistamines and new-generation topical nasal steroids often used by otorhinolaryngologists demonstrate a good safety profile without systemic side effects. In summary, allergic rhinoconjunctivitis represents a common disease pattern that can be treated effectively. Once it is diagnosed correctly targeted treatment results in improved patients' quality of life quickly.

Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. Allergic conjunctivitis is often underdiagnosed and consequently undertreated. Basic and clinical research has provided a better understanding of the cells, mediators, and immunologic events, which occur in ocular allergy. New pharmacological agents have improved the efficacy and safety of ocular allergy treatment. An understanding of the immunologic mechanisms, clinical features, differential diagnosis, and treatment of ocular allergy may be useful to all specialists who deal with these patients. The purpose of this review is to systematically review literature underlining all the forms classified as ocular allergy: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratocongiuntivitis, contact allergy, and giant papillary conjunctivitis.

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.