Dry eye disease (DED), one of the most common conditions encountered in the ophthalmology clinic, is a multifactorial disease of the tears and ocular surface that can result from abnormalities in the tear film, ocular surface, and/or somatosensory pathways.1
DED symptoms are a cause of significant morbidity, particularly as a source of chronic ocular pain often described as “dryness,” “grittiness,” “burning,” and/or “irritation,” to name a few descriptors.
Risk factors and psychological components of DED
Various risk factors have been identified for DED, including demographics (e.g., older age, female gender), medications (e.g., anti-histamines, anti-depressants), and co-morbidities (e.g., autoimmune diseases, pain disorders such as fibromyalgia and migraine, and mental health disorders).
It is not surprising that these factors have been related to DED as age, gender, medical co-morbidities, and environmental exposures have all been shown to influence the perception of pain (one important aspect of DED) in addition to the function of glands (e.g., lacrimal, meibomian) that produce tear components.
Psychosocial factors can also impact the pain experience, such as anxiety, depression, inadequate social support, and perceived lack of control over pain have all been associated with increased pain levels. As such, understanding and acknowledging the link between DED, pain, and mental health conditions is an important task for eyecare providers who treat individuals with DED.
Dry eye disease, pain, and mental health
It is important to acknowledge that ocular pain is a big component of DED. Ocular pain can arise from nociceptive sources, such as low tear production and ocular surface inflammation, as is often seen in individuals with autoimmune conditions such as Sjögren's syndrome.2
Ocular pain can also arise from neuropathic sources, with an ocular phenotype that presents with symptoms that outweigh the signs of the disease. In addition, neuropathic ocular pain symptoms are often characterized as “burning,” and individuals report evoked pain due to wind and light.3
Psychosocial factors have been associated with both types of ocular pain. Anxiety disorders, major depressive disorder (MDD), and post-traumatic stress disorder (PTSD) are among the mental health conditions that have been linked to DED prevalence and severity.4
Furthermore, a neuropathic DED phenotype has been linked to systemic pain disorders that are often co-morbid with mental health dysfunction, such as fibromyalgia and chronic migraine, among others.4,5,6,7
A recent study on DED and co-morbid mental health diseases
A systematic review of 32 studies by Basilious et al. examined co-morbidity between DED (variably defined) and mental health diseases (31 MDD, 19 anxiety) and found that a large proportion of individuals diagnosed with DED were also diagnosed with co-morbid MDD (prevalence = 40%, confidence interval [CI] 0.29 to 0.52).8
In fact, there were 1.81 times higher odds of a co-morbid MDD diagnosis in the DED group compared to controls (odds ratio [OR]=1.81, CI 1.61 to 2.02, p<0.05). Similar co-morbidity was noted with respect to anxiety, with a 39% prevalence of anxiety across studies (CI 0.15 to 0.64) and 2.32 times higher odds of a co-morbid anxiety diagnosis in individuals with DED compared to controls (OR=2.32, CI 1.67 to 3.23, p<0.05).
Using a variety of measures, some specific for pain, others that incorporate pain and other symptoms, such as visual disturbances and tearing (including the Ocular Surface Disease Index [OSDI] and 5 Item Dry Eye Questionnaire [DEQ5]), Basilious also found that ocular symptoms scores across studies were consistently associated with MDD (effect size [ES] = 0.43; CI 0.31 to 0.55) and anxiety (ES = 0.41; CI 0.32 to 0.50) severity scores.8
Signs and symptoms of DED and mental health disorders
Unlike the consistent link between DED symptoms, co-morbid pain conditions, and mental health indices, DED signs (consisting of a variety of measures, including tear production, tear stability, and epithelial disruption) have not been clearly related to non-ocular pain and mental health indices.
In the meta-analysis noted above, seven studies captured DED signs, and no significant correlations were noted between depression and anxiety severity with tear stability (tear breakup time [TBUT]), production (Schirmer's test), or epithelial disruption (fluorescein staining).8
Several hypotheses have been raised on why symptoms relate to non-ocular pain and mental health disorders more so than signs. One theory hypothesizes that the presence of mental health disorders, such as intense anxiety, may influence the perception of ocular symptoms (e.g., pain, blurry vision, etc.) with an impact on subjective reporting.
Others point to potential shared mechanisms, such as central nervous system abnormalities, that may underlie the noted co-morbidities.9 These questions remain an area in need of further study.
The “coping” connection
Beyond mental health disorders, other factors related to mental health have also been examined in relation to DED. In particular, reliance on dysfunctional (e.g., negative or passive) coping strategies, thoughts and actions used by individuals to deal with a particular stressor,10 have been found to be associated with DED symptoms but not sign severity.11
While several types of coping strategies exist, active coping strategies, which are helpful in overcoming pain, are characterized by reliance on oneself to function in spite of pain (e.g., task persistence or positive self-statements).
On the other hand, dysfunctional strategies allow daily activities to be impeded or changed due to perceived pain (e.g., relying on external aid during painful tasks, pain avoidance, and catastrophizing) and can thus lead to a sense of helplessness in the face of uncontrolled pain.12
The link between mental status, coping strategies, and ocular pain
One study of 194 US veterans seeking care at a Veterans Affairs (VA) eye clinic found that reliance on catastrophizing—a negative coping strategy characterized by rumination, magnification, and helplessness,13 as measured by the Pain Catastrophizing Scale (PCS)—was positively correlated with several DED symptom severity indexes.
This includes the DEQ5 (r = 0.41, p < 0.0005), OSDI (r = 0.40, p < 0.0005), and Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye, r = 0.48, p < 0.0005). It is important to note that clinical signs of disease (TBUT, Schirmer’s, and staining) did not correlate with PCS scores.11
These findings suggest that mental status and coping strategies may influence the way an individual perceives stimuli on their ocular surface, even in instances where abnormalities are not detected on exam. These findings emphasize the importance of evaluating mental status and discussing healthy coping strategies when treating individuals with ocular pain.
Conclusion
An abundance of research suggests a link between DED symptoms, especially pain-related symptoms, non-ocular pain co-morbidities, and mental health dysfunction. While the majority of currently utilized therapies for DED symptoms focus on improving ocular surface and tear health, research suggests that, in appropriate individuals, a more holistic approach is needed.
Specifically, there may be utility in targeting behavioral and psychosocial variables that influence the perception of pain to aid in symptomatic control of ocular symptoms. Additional research is needed to explore which mental health interventions (e.g., cognitive behavioral therapy [CBT] and meditation) are optimal in addressing ocular symptoms.
Nevertheless, the associations summarized above suggest that comprehensive and multidisciplinary approaches may be necessary to achieve optimal therapeutic outcomes in individuals with severe or refractory DED symptoms.
