Neuropathic Ocular Pain: An Important Yet Underevaluated Feature of Dry Eye

A Galor; RC Levitt; ER Felix; ER Martin; CD Sarantopoulos


Eye. 2015;29(3):301-312. 

In This Article

Abstract and Introduction


Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.


Per the Definition and Classification Subcommittee of the International Dry Eye WorkShop (DEWS), dry eye is 'a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.'[1] Beyond the eye, the disorder also involves the Lacrimal Functional Unit,[2] consisting of the ocular surface, the main lacrimal gland, and the interconnecting innervation.

Population-based studies in various US cities have utilized questionnaires (different questionnaires for different studies) to evaluate the frequency of dry eye, with an estimated prevalence of ~15%.[3–7] Similar studies conducted in several countries around the world including Germany,[8] Australia,[9,10] Japan,[11–14] India,[15] Thailand,[16] and Indonesia[17] have resulted in similar prevalence estimates. As summarized in the DEWS report, the prevalence of dry eye is most likely in the range of 5–30% of the population aged ≥50 years.[18] Dry eye complaints are dominated by various symptoms including blurred vision, irritation, and pain (eg, burning, aching); collectively causing great morbidity. Symptoms associated with dry eye are a leading cause of visits to optometry and ophthalmology clinics and its treatment has significant cost implications.[19,20] Dry eye adversely affects quality of life as its symptoms interfere with daily activities such as driving, working, reading, and watching television.[21] In a similar manner, studies using the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire have found that dry eye negatively affects social, physical, and mental functioning.[22,23]

Currently, clinicians split dry eye into two main categories: aqueous deficiency and evaporative, as reviewed in the Definition and Classification DEWS report.[1] Dry eye treatments are generally geared toward improving these tear film components based on a long-standing paradigm that tear dysfunction underlies dry eye symptoms. Aqueous deficiency is typically addressed with tear replacement therapy and punctal occlusion, whereas evaporative dry eye is managed with lid hygiene and topical and/or oral antibiotics (used for nonantibiotic properties such as their anti-inflammatory effects[24]). In common to both, anti-inflammatory agents are often used (for varying durations) to treat the inflammatory component of dry eye.

Although several studies have reviewed that neurosensory dysfunction can be a component of dry eye symptoms in some patients,[25,26] this aspect of dry eye is not routinely tested for (or treated) in the clinical setting. A better understanding of the neuropathophysiology underlying dry eye pain will facilitate the development of novel therapies that can target these mechanisms. This review will summarize research findings on neurosensory dysfunction in dry eye and discuss how they may affect the diagnosis and treatment of dry eye pain.