Comorbid Psychiatric and Inflammatory Conditions in Dry Eye Disease


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BDI beck depression inventory, EPDS Edinburgh postnatal depression scale, GDS geriatric depression scale, PHQ-2 patient health questionnaire-2, PHQ-9 patient health questionnaire-9, WHO-5 World Health Organization well-being index

Mrs. G also carried a diagnosis of fibromyalgia. Fibromyalgia is a disease characterized by centralized pain manifesting as multifocal pain in different body regions at different times, not fully explained by injury or inflammation. Interestingly, some patients with fibromyalgia have also been found to have small fiber neuropathy on biopsy [5]. While widespread musculoskeletal pain is a hallmark of fibromyalgia, insomnia, cognitive disturbances (e.g., forgetfulness, decreased concentration), headache, irritable bowel syndrome, depression [6], and dry eye symptoms have also been found to be more common in patients with fibromyalgia [7, 8].

How Often Does Depression Coexist with Dry Eye?

Depression has been found to coexist with dry eye in a number of different population-based studies from Beijing [9], Korea [10], and the Netherlands [11]. In two population-based cross-sectional studies involving 2113 patients from Beijing and Korea, the results showed that depression correlated with dry eye symptoms (gritty, sandy, burning, dry), but did not correspond with dry eye signs of tear breakup time (TBUT) or Schirmer’s test score [9, 10]. In a study utilizing the US Veterans Affairs (VA) national database, both post-traumatic stress disorder (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.91–1.94) and depression (OR 1.92, 95% CI 1.91–1.94) were found to increase the risk of a dry eye diagnosis. These findings were robust when considering the effect of age, gender, and concomitant use of antidepressants and anxiolytics [12]. Regarding pain, in a cross-sectional study of 425 patients, the frequency of dry eye symptoms was higher in the subset of study participants with a chronic pain syndrome (irritable bowel syndrome (IBS), chronic pelvic pain, or fibromyalgia) than without it, but ocular signs were no worse [11].

What Are the Treatment Options in Comorbid Psychiatric and Pain Disorders?

Treatments for psychiatric conditions, like depression and anxiety, in patients with dry eyes are best approached by integrating pharmacological and nonpharmacological therapies (patient education, exercise therapy, cognitive behavioral therapy) while keeping the patient active in the process. These are based on the experiences in treating patients with fibromyalgia.

Pharmacologic Treatment

Pharmacologic treatments generally work by reducing the activity of excitatory neurotransmitters (such as glutamate) (e.g., pregabalin, gabapentin) or by increasing the activity of inhibitory neurotransmitters, such as norepinephrine, serotonin, and γ-aminobutyric acid or GABA (e.g., serotonin-norepinephrine reuptake inhibitors, which include duloxetine, milnacipran). After a diagnosis of depression or anxiety has been established, the next steps should be to determine whether treatment is needed or not, based on the clinical extent of severity, distress or impairment, and the patient’s preference. If pharmacologic therapy is initiated, SSRIs or SNRIs are usually the first-line therapies given their reasonable side effect profile [13]. Table 10.2 gives a comparison of the SSRIs and SNRIs available in the treatment of depression and anxiety. After initiation of medication, changes in mood can be seen within 1–2 weeks [1416].

Table 10.2
Pharmacologic treatment for fibromyalgia-associated pain/anxiety which may be considered for ocular surface patients


Initial daily dose (oral, mg)

Daily dose range (oral)

Side effect profile/characteristics




Insomnia, agitation, GI upset, diarrhea




Insomnia, agitation, weight changes, takes weeks for effect




Mild sedative, weakly anticholinergic




Can prolong QT interval, lower risk of insomnia and agitation




Useful for treatment of comorbid pain conditions




Increased blood pressure (diastolic) and heart rate with increasing doses, greater risk of insomnia/agitation, useful for treatment of comorbid pain conditions


10 (divided doses)

10–60 (divided doses)

A nonbenzodiazepine anxiolytic, ineffective for comorbid major depression




Appetite stimulant, useful for anxiety with insomnia, sedating, atypical antidepressant




Extrapyramidal symptoms, weight gain, metabolic side effects


75 (divided doses)

75–200 (divided doses)

Anticholinergic side effects, potential cardiotoxicity, TCA


50 (bedtime)

25–50 TID

Anticholinergic side effects


10 (bedtime)


Anticholinergic side effects, dry mouth, dry eyes, somnolence, rarely tachycardia


5 (bedtime)


Anticholinergic side effects, dry mouth, dry eyes, somnolence, rarely tachycardia

Drugs listed in Table 10.2 have also been found effective in the treatment of fibromyalgia-associated pain and may be considered in patients with ocular surface pain. Currently, the best-studied medications include certain SNRIs (e.g., duloxetine and milnacipran), tricyclic antidepressants (e.g., amitriptyline), and anticonvulsants (e.g., gabapentin and pregabalin) [1719]. Interestingly, other drugs frequently used to treat pain such as nonsteroidal anti-inflammatory drugs, opioids, and corticosteroids have not been shown effective in treating fibromyalgia pain. In fact, opioids have been shown to worsen fibromyalgia-related hyperalgesia and pain in other centralized pain states [20]. It is thought that the opioid system is hyperactive in fibromyalgia patients, possibly explaining why opioids are ineffective at treating pain symptoms. As such, another promising treatment in fibromyalgia is low-dose naltrexone [21]. Naltrexone is thought to suppress microglial activity and, thereby, decrease the production of proinflammatory factors, such as cytokines, excitatory amino acids, and nitric oxide, which can cause hyperalgesia, fatigue, and other symptoms of fibromyalgia [22, 23]. In addition, trigger point injections may be beneficial in the treatment of fibromyalgia [24, 25].

Nonpharmacological Therapies

The best-studied nonpharmacological therapies are education, cognitive behavioral therapy, and exercise. For the initial treatment of unipolar major depression, numerous studies have shown that the efficacy of psychotherapy and pharmacologic treatment exceeds pharmacologic treatment alone. In fibromyalgia, other treatments include chiropractic manipulation, tai chi, yoga, acupuncture, and myofascial release therapy [26, 27]. Both transcutaneous and central neurostimulatory therapies have also been used to treat pain with some success in fibromyalgia [28, 29].

What Is an Appropriate Management of This Patient?

In this patient, a multi-specialist approach is required. The ophthalmologist should work with the patient’s primary care physician and encourage a referral to a mental health professional. Despite good cross-sectional data associating mental illness and dry eye, no longitudinal data exist to guide therapy in this case. For example, it is not known what effect treating chronic non-ocular pain and depression/anxiety will have on dry eye symptoms. As such, it is advisable for the ophthalmologist to provide local therapy to improve ocular surface health, as needed, and to work in conjunction with other specialties that can address the non-ocular conditions associated with dry eye.

Case #2: Aqueous Deficient Dry Eye in the Setting of Systemic Immune Disease

A 49-year-old female with history of inflammatory arthritis on hydroxychloroquine therapy presented to the eye clinic with complaints of decreased vision, burning, and redness in both eyes. She uses preservative-free artificial tears up to 6–8 times a day without relief. She states her symptoms are worse upon awakening and while working on the computer for her secretarial job. Past medical history is significant for back and joint pain, which have been well controlled with hydroxychloroquine and ibuprofen as needed. She is otherwise healthy and takes no other medications.

On examination, her best-corrected visual acuity is 20/25 OU with normal intraocular pressures. Osmolarity testing reveals a value of 308 mOsm/L OD and 315 mOsm/L OS. Evaluation of the external periocular skin shows no rashes or skin findings. On slit lamp examination, moderate telangiectasias are observed on her lower eyelid margins, and the bulbar conjunctivas have mild hyperemia. On fluorescein examination, tear film breakup time (TFBUT) is 7 s and 9 s in the right and left eye, respectively. The patient has a decreased tear lake OU with 3+ punctate epithelial erosions in the inferior cornea. Schirmer’s testing with anesthesia reveals 4 mm of wetting OD and 3 mm of wetting OS after 5 min. InflammaDry (RPS Technologies, Tampa) is positive with a moderate-strength band in both eyes. The remaining ocular examination is otherwise unremarkable.

What Do These Findings Mean?

These examination findings suggest that the patient has aqueous deficient dry eye (DE). The definition of dry eye provided by the 2007 international dry eye workshop (DEWS) report is “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear firm instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [30].

Given its multifactorial nature, no single test can identify all dry eye patients. A number of different diagnostic tests are used to evaluate different components of the ocular surface.

Tear Volume

Tear film volume can be examined using the slit lamp to observe the tear meniscus. An inferior tear meniscus height of less than 1 mm (in the absence of significant conjunctivochalasis obliterating the meniscus) suggests aqueous deficiency [30]. High-resolution anterior segment optical coherence tomography (OCT) has been more recently used to assess the inferior tear meniscus. The meniscus is first imaged with the machine, and the image is then used to calculate inferior tear meniscus volume [31].

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Jan 14, 2018 | Posted by in OPHTHALMOLOGY | Comments Off on Comorbid Psychiatric and Inflammatory Conditions in Dry Eye Disease

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