Ocular surface allergy is a group of allergic diseases involving the ocular surface, which are common worldwide and share a common pathogenesis and inflammatory manifestations with systemic allergic diseases. The incidence varies greatly from 5% to 22% in different regions due to different geographical and medical conditions, but the actual incidence is even higher than these statistics. In recent years, the incidence of ocular surface allergy has increased significantly with changes in the natural environment, contact lens wear and other factors, and thus has received widespread attention. The pathophysiology of ocular surface allergy The ocular surface is directly exposed to the external environment and comes into direct contact with allergens, making it susceptible to various allergic diseases. The normal conjunctiva contains various types of cells involved in allergic reactions, including mast cells, antigen-presenting cells, T lymphocytes, eosinophils, basophils and fibroblasts, which cause clinical symptoms through the release of various inflammatory mediators after sensitization. At the same time, conjunctival epithelial cells also express a variety of cytokines and inflammatory mediators, which play an important role in the development and progression of chronic allergic eye disease. Ocular surface allergy is dominated by IgE-mediated type I allergic reactions, with the participation of T-lymphocyte-mediated type IV allergic reactions. type I allergic reactions involve a pathological process divided into two phases. The first phase: antigen binds to IgE and activates mast cells to release mediators within a few minutes or ten minutes, lasting for several hours; the main mediator of the reaction is histamine, which binds to histamine receptors, leading to increased vascular permeability, smooth muscle contraction, and enhanced glandular secretion. Second phase: after the mast cells are activated for 2-6 hours and lasts for a longer period of time. The main mediators involved are lipid mediators, such as prostaglandins (PG), leukotrienes (LK), thromboxane (TAX) and platelet-activating factor (PAF), etc. The main effects produced increase the inflammatory response, smooth muscle contraction, increased vascular permeability, and further enhanced glandular secretion, resulting in pain when the response is severe. Normal human conjunctiva is rich in mast cells, about 5000/mm2, with high-affinity IgE receptors on the cell surface, which are the most important cells in IgE-mediated allergic reactions. Activated mast cells release large amounts of histamine early in the allergic reaction, binding to histamine receptor 1 (H1r), producing the main symptom of itchy eyes; binding to histamine receptor 2 (H2r), causing vasodilation, tissue congestion, edema, and increased secretion. Recent studies have revealed that T lymphocytes play an important role in initiating and regulating allergic reactions; eosinophils and basophils are involved in the pathogenesis of ocular surface allergy and are the main cells responsible for the recurrence of symptoms in the chronic phase. Classification and clinical manifestations According to different clinical manifestations and pathogenesis, common ocular surface allergies are divided into five categories: seasonal and perennial allergic conjunctivitis, spring cicatricial conjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and contact conjunctivitis.1. Seasonal Allergic Conjunctivitis (SAC) and Perennial Allergic Conjunctivitis (PAC) （Seasonal Allergic Conjunctivitis (SAC) and Perennial Allergic Conjunctivitis (PAC) Epidemiology SAC is seasonally related and is the most common form of allergic conjunctivitis, accounting for 25% to 50%; in the United Kingdom, 10% to 15% of the total population suffers from SAC; in the United States, SAC is the second most common condition, accounting for 9.4%; to date No relevant epidemiological data are available in China. The incidence of PAC is generally considered to be lower than that of SAC, and SAC and PAC mostly begin in childhood, with a male predominance. It has been found that the susceptibility to allergic conjunctivitis has a genetic predisposition, and the main links involved are the regulation of IgE production and the binding of IgE to specific antigens. If one parent is atopic, the next generation is four times more likely to develop allergic conjunctivitis than normal, and if both parents are atopic, the odds are 10 times higher than normal. The antigens that cause SAC are mainly outdoor seasonal antigens such as pollen, grass and leaves, and mold spores; the antigens that cause PAC are mainly indoor perennial antigens such as dust mites, molds (Aspergillus flavus, Aspergillus fumigatus, and Penicillium spp.) and animal fur dander. The pathological mechanism of SAC and PAC is mainly IgE-mediated type I metamorphosis, the main cells involved in the reaction are mast cells, and the main mediators are histamine and prostaglandins, etc. Recent studies have found that leukotrienes released from eosinophils and histamine released from basophils are also involved in the pathological process of inflammation. Most patients with SAC have a history of antigenic exposure, some of them have a family history of allergic disease, and about 40% of patients have a combination of allergic rhinitis. patients with SAC mainly present with sudden onset of bilateral eye itching, mild edema of the eyelids and bulbar conjunctiva, and small papillary hyperplasia of the upper lid conjunctiva. The cornea is generally unaffected except in acutely ill patients.PAC has a milder clinical presentation than SAC, but the signs and symptoms persist. Laboratory tests: Conjunctival scraping cytology reveals eosinophils; increased tear IgE content; skin allergen test helps to find allergens. 2. Spring Catarrh Keratoconjunctivitis (VKC) Epidemiology VKC accounts for about 0.5% of ocular allergic diseases, 60% of patients are between 11 and 20 years old. VKC is common in spring and is associated with more plant pollen in spring, but it also occurs in other seasons, and a few patients can have the disease all year round. The incidence is generally higher in hot flushes. The pathomechanism of VKC is mainly type I metaplasia and is associated with type IV metaplasia, which is a metaplasia mediated by mast cells, eosinophils and lymphocytes. Studies have shown that patients have reduced levels of histaminase in their tears compared to normal subjects, resulting in impaired local histamine metabolism and elevated histamine levels. Clinical presentation and diagnosis VKC is clinically divided into three types: lid conjunctival type: lesions mainly occur in the upper lid conjunctiva. Bulbar conjunctival type: lesions mainly occur in the bulbar conjunctiva. The typical clinical manifestations of VKC are: bilateral onset, persistent itching, tearing, foreign body sensation, mucus discharge, photophobia with corneal involvement; lid conjunctiva congestion, cobblestone (paving stone) like papillae, and gelatinous nodules in the bulbar conjunctiva near the corneal limbus. The literature reports that 50% of patients have keratoconus, and in severe cases, shield-shaped corneal ulcers may form. Approximately 3% of patients can become blind due to keratopathy. Laboratory tests: eosinophils are seen in conjunctival scrapings, histamine and trypsin-like enzymes are elevated in the patient’s tears, lactoferrinase is decreased, and lysozyme levels are normal. 3, Giant Papillary Conjunctivitis (GPC) epidemiology GPC is known as a “medical disease”, associated with corneal contact lenses, prosthetic eyes, exposed suture irritation, etc., was first reported in 1950. It has been shown that GPC can occur in 1-5% of patients wearing rigid corneal contact lenses and 15% of patients wearing soft corneal contact lenses. Pathogenesis GPC is mainly a combination of type I and type IV metaplasia, and is an inflammatory process mediated by mast cells and lymphocytes. Conjunctival infiltration of basophils, eosinophils, plasma cells and lymphocytes is seen. The clinical manifestations and staging of GPC are similar to VKC in terms of itchy eyes and mucus discharge, but the itch is less severe than the latter. There are 4 stages according to symptoms and signs: stage 1: itchy eyes, mild lid conjunctival congestion, tiny papillae hyperplasia; stage 2: itchy eyes, more mucous discharge, upper lid conjunctival congestion, irregular papillae hyperplasia; stage 3: moderate to severe itchy eyes, more mucous discharge, upper lid conjunctival papillae hyperplasia, some papillae larger than 1 mm in diameter, upper lid congestion and edema. stage 4: severe itchy eyes, large amount of mucous discharge, upper lid Conjunctival papillae hyperplasia, larger than 1 mm, some mushroom-shaped with necrosis at the tip, fluorescent staining. If the cause can be removed before stage 2, GPC can gradually disappear; for lesions above stage 2, even if the cause is removed and inflammation is controlled, their proliferative changes are difficult to completely subside. 4, Atopic Keratoconjunctivitis (AKC) epidemiology According to statistics, 3% of the population suffers from allergic dermatitis, of which 25%-42% involve the eye. Most patients have a family history of atopic dermatitis and are often associated with eczema-like skin changes. The pathomechanism is a chronic allergic inflammatory process. Early in the course of the disease, conjunctival cupped cells proliferate and mucous secretions increase; after the lesion persists, cupped cells decrease, conjunctival epithelial pseudonodules form, eosinophils, mast cells and lymphocytes infiltrate the conjunctiva, and scar tissue forms. Clinical manifestations of AKC often involve the lower lid, with a chronic inflammatory process that is easily prolonged and has heavier symptoms than other allergic ocular surface diseases, aggravated in summer and winter. Patients are mostly 20-50 years old, with more males, and 95% of patients have combined skin eczema. The main clinical manifestations are itchy eyes, astringent eyes, heavy eyelids, chronic eczema of the eyelids, congestion of the lid conjunctiva, or edema and pallor with mucous secretions, often accompanied by corneal epithelial lesions or corneal ulcer formation, which can lead to blindness in severe cases, and cataract or uveitis in a few patients; some patients have abnormal tear secretion. Contact hypersensitivity is an allergic conjunctivitis caused by local medications or exposure to chemicals, with a rapid onset and a clear history of exposure, and is called drug allergic conjunctivitis or contact conjunctivitis. Common ocular sensitizing drugs include: atropine, thiamethoxam, sulfonamide, iodoside, and sodium cromoglycate. All four types of allergic reactions may be involved in the reaction, but types I and IV are the most common. Patients have a clear history of drug administration with itchy eyes, flushed and edematous eyelids; diffuse conjunctival congestion and edema, with visible papillae and follicular hyperplasia. Severe patients develop superficial punctate keratitis and even iritis. The symptoms resolve after discontinuation of the drug and subside after several weeks.