The multifaceted aspects of ocular allergies: Phenotypes and endotypes

Like the lung, skin, and nose, the external eye is a common target of allergic inflammation. Ocular allergy (OA) represents a collection of underestimated diseases of the eye observed in children and adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, but for a few patients, long term inflammation may remarkably reduce the visual function. Evidence suggests that other co-participant systems, including epigenetic, genetic, environmental, individual factors, sex hormones, and the central and autonomic nervous systems may influence the ocular response from distant sites. This is consistent with the concept that the eye is an organ fully integrated with the rest of the body and that the therapeutic approach should be holistic, dynamic, and personalized. For instance, androgens and estrogens binding to receptors on the ocular surface and the continuous cross-talking of neuromediators and growth factors with immune cells act to maintain the ocular surface homeostasis in response to environmental challenges. The immune system links and regulates the response of the ocular surface. Complex and incompletely understood mechanisms influence the innate and adaptive immune responses and generate different OA phenotypes and endotypes discussed in the present review.