Factors affecting the prevalence, severity, and characteristics of ocular surface pain

Abstract

Introduction: Ocular surface pain has been traditionally lumped under the umbrella term "dry eye" (DE) but is now understood as its own entity and can occur in the absence or presence of tear dysfunction. Identifying patients at risk for the development of chronic ocular surface pain, and factors contributing to its severity are important in providing precision medicine to patients.

Areas covered: In this review, we discuss factors linked to the presence and severity of ocular surface pain, including eye related features, systemic characteristics, and environmental findings. We discuss corneal nerves, whose anatomic and functional integrity can be characterized through in vivo confocal microscopy images and testing of corneal sensitivity. We review systemic diseases that are co-morbid with ocular surface pain, including physical and mental health diagnoses. Finally, we identify environmental contributors, including air pollution, previous surgeries, and medications, associated with ocular surface pain.

Expert opinion: Intrinsic and extrinsic factors contribute to ocular surface pain and must be considered when evaluating an individual patient. These factors can inform the suspected etiology of the pain, and guide management decisions such as tear replacement or medications targeting nerve pain.

Keywords: dry eye; hyperalgesia; nerve sensitization; neuropathic pain; nociceptive pain; ocular surface pain; pain.

Figure 1:. Ocular surface pain is a complex phenomenon with many contributory factors.

These include factors that are related to the ocular surface itself, such as the anatomy and function of corneal nerve fibers that can be visualized using confocal microscopy and assessed by measuring corneal sensitivity. Further, non-ocular factors may influence ocular surface pain presentation, including the presence of systemic co-morbidities (fibromyalgia, migraine), gender, sleep quality, emotional state, and coping mechanisms. The external environment may also contribute to ocular surface pain, with factors such as weather and air pollution, medication use, and previous surgeries influencing pain.

Figure 2:. Neuropathic pain develops due to injury induced ocular surface inflammation.

In the setting of an injury, various resident and circulating immune cells (e.g., mast cells, neutrophils, and macrophages) can release mediators (e.g., tumor necrosis factor, prostaglandin E, histamine, and interleukin 1) that are sensed by corneal nerves, leading to a change in peripheral nerve anatomy and function. Subsequently, changes can occur in ascending central pathways through the trigeminal nucleus caudalis (TNC), thalamus, and ultimately to higher pain processing centers in the cerebral cortex.