Nociceptors respond to noxious stimuli and transmit pain signals to the central nervous system. In the cornea, the nociceptors located in the most external layer provide a myriad of sensation modalities. Damage to these corneal nerve fibers can induce neuropathic pain. In response, corneal nerves become sensitized to previously non-noxious stimuli. Assessing corneal pain origin is a complex ophthalmic challenge due to variations in its causes and manifestations. Current FDA-approved therapies for corneal nociceptive pain, such as acetaminophen and NSAIDs, provide only broad-acting relief with unwanted side effects, highlighting the need for precision medicine for corneal nociceptive pain. A few targeted treatments, including perfluorohexyloctane (F6H8) eye drops and Optive Plus (TRPV1 antagonist), are FDA-approved, while others are in preclinical development. Treatments that target signaling pathways related to neurotrophic factors, such as nerve growth factors and ion channels, such as the transient receptor potential (TRP) family or tropomyosin receptor kinase A, may provide a potential combinatory therapeutic approach. This review describes the roles of nociceptors in corneal pain. In addition, it evaluates molecules within nociceptor signaling pathways for their potential to serve as targets for efficient therapeutic strategies for corneal nociceptive pain aimed at modulating neurotrophic factors and nociceptive channel sensitivity.

Dry eye disease (DED) is a common condition that can be associated with cataract surgery, requiring pre- and postoperative considerations. Pre-existent DED and disruption of the tear film homeostasis due to incisional corneal nerve damage, intra-operative ocular surface drying, microscope phototoxicity, or the toxic effects of preservatives and active ingredients of postoperative drops or a combination thereof, represents a potential mechanism for worsening or developing DED after cataract surgery. Recent diagnostic advancements have enabled us better to understand the pathophysiology of DED after cataract surgery. For patients with pre-existing DED before cataract surgery, early intervention can improve surgical outcomes. In contrast, failure to recognize DED risk factors or subtle signs can result in inaccurate refractive measurements, poor surgical outcomes, including serious complications, worsening of dry eye symptoms, patient dissatisfaction, and decreased quality of life. This review presents an overview of the perioperative management of DED in patients undergoing cataract surgery with an emphasis on pre-operative diagnosis and treatment, and its impact on improving surgical refractive outcomes and decreasing complications.