GPN-600X120-Above Article-GPN EdgePro 2019

Dry Eye Disease is defined by The Tear Film & Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) as ‘‘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) Symptoms of ocular surface disease can significantly impact the quality of life, due to chronic pain. Dry eye has been associated with psychiatric disorders including depression and anxiety. An increasing number of studies support this association. 

Kitazawa, et al, used a team of ophthalmologists and psychiatrists to assess subjects for OSD and psychiatric disorders.(2) Ophthalmologists used Tear Break Up Time (TBUT), Schirmer testing, fluorescein staining, and presence of symptoms identified using the Dry Eye Related Quality of Life Score (DEQ) to assess the level of ocular surface disease severity. Psychiatric assessments included interviews, Mini International Neuropsychiatric Interview (MINI), and standardized testing including Japanese versions of the Montgomery-Asberg Depression Scale (MADRS), Quick Inventory of Depressive Symptomatology-Japanese version (QIDS-SR16), and the Japanese version of the Hamilton Rating Scale for Anxiety (HAM-A). Forty subjects were initially enrolled but 14 dropped out due to the secondary psychiatric evaluation. The average age was 61.3 (SD 18.1) years, and 75 were female. All patients received treatment for dry eye. After a psychiatric assessment, 6 of 40 (15.0%) of patients exceeded the threshold of MADRS. Eighteen of 35 (51.4%) exceeded the threshold for QIDS for depression. Five of 34 (14.7%) of the subjects exceeded the threshold score of HAMA for having an anxiety disorder. Only two patients had been treated for depression prior to study enrollment. Patients were divided into two groups based upon the three psychiatric assessment tools, and all three were correlated with a significantly higher DEQS score based upon symptomatology but were not found to be different using objective methods (TBUT, Schirmer testing and Fluorescein staining). 

This phenomenon of correlation with subjective symptoms more than objective symptoms has also been reported by Labbe, et al.(3) Li et al. reported that the Zung Self Rating Anxiety Scales scores were correlated with the OSDI and educational level, and the Zung Self Rating Depression Scales scores were found to be correlated with OSDI in the DED group.(4) Hallak et al. found DED symptom scores and depression scores evaluated from the Beck Depression Inventory were statistically significantly different between the dry eye and control group.(5)

Other studies have reported significant correlation of objective signs. Kim et al. found depression assessed using the Short Geriatric Depression Scale (SGDS-K, Korean version) was associated with DED symptoms in elderly subjects.(6) Mrugacz et al. reported that tear levels of interleukin (IL)-6, IL-17, and tumor necrosis factor-a, which had significant correlation with dry eye severity, were higher in depressed patients than in the control group.(7)

Another study recently published evaluated patients newly diagnosed with mood disorders using anterior segment optical coherence tomography.(8) The 40 patients with depression, 35 anxiety patients, and 37 controls had no previous history of psychiatric drugs or topical ophthalmic drop use prior to the study. Psychiatric assessment was performed using the Beck Depression Index and Beck Anxiety Inventory, administered by a psychiatrist. The ocular surface disease index (OSDI) was used to assess dry eye. Objectively, TBUT, Oxford scores of corneal staining, and Schirmer’s testing were used, as well as anterior segment optical coherence tomography measurement of tear meniscus heights (TMH), tear meniscus depths (TMD) and tear meniscus areas (TMA). This study did find differences in the objective measures. Schirmer’s test, TBUT, and MD, TMH, and TMA values were significantly lower in the mood disorder groups than the control group. OSDI and Oxford scores were significantly higher than controls and were significantly lower in anxiety and depression groups compared with control groups. Again, these differences were noted prior to treatment using psychiatric medications.

There are a few hypotheses regarding the association between dry eye and psychiatric disorders. A connection between serotonin function and secretion of tears from the lacrimal gland has been suggested. One study reported tear serotonin concentration positively correlated with symptoms and signs of dry eye.(9) Sharif, et al, suggested that disturbances of the serotonin receptors located within conjunctival epithelium may influence meibomian glands, leading to tear film deficiency in depression patients.(10) Higher tear serotonin levels have been reported in those with depression.(11) Another study found the concentration of neuropeptide Y (NPY) was low in the tear fluid of DED patients. This NPY has an anti-anxiolytic effect.(12)

Depression is associated with comorbidities such as hypothyroidism, systemic lupus erythematosus, myasthenia gravis, liver diseases, hypertension, diabetes mellitus, cardiac disease, gastrointestinal disorders, rheumatic diseases, and systemic medications.

The medications used to treat mood disorders have been implicated in the etiology of dry eye. The chronic symptomatology of dry eye may increase anxiety about patient’s eyes, much like chronic pain. Chronic pain is a potent stress factor affecting mood and is associated with mood disorders.(13) Depression and pain use similar biological pathways and neurotransmitters including adrenaline and serotonin.(14) The increase in doctor visits, cost of medications and the required frequency of using such medications may also be a factor. 

Patients may be reluctant to initiate treatment for depression due to fear of these medications exacerbating their dry eye problems. A google search on dry eye and depression revealed several postings of people asking this question on various social media platforms. Hopefully, these people also asked their doctor about their concerns. Symptoms of a somatic disease may worsen when patients have depression.(15,16)

When suggesting a patient may benefit from psychiatric consultation, the patient may become defensive, thinking the doctor is implying the problem is “all in their head”. I often start this conversation from a chronic pain perspective explaining that I am concerned that chronic pain often results in depression and I need another doctor’s help with that side of treatment. Alternatively, I may suggest that they appeared “really sad” at their last several appointments and I am concerned that their mood might be affecting the healing process.  People that are “happier” are less likely to be affected by subjective dry eye symptoms,(17) and I need help from another doctor to help their eyes heal.   

It is important to note that as eye doctors, it is our job to treat the ocular surface disease but not the mood disorders. Any patient that refers to suicidal ideation must be taken seriously, and immediate action must be taken to obtain a further evaluation by a psychiatrist. Any comments regarding suicide, even sarcastic or off-handed remarks, should be addressed directly by requesting confirmation that the patient has had suicidal thoughts. It is best to refer them to the emergency room for evaluation.


  1. Craig JP, Nichols KK, Nichols JJ, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15:276–283. 
  2. Kitazawa M, Sakamoto C, Yoshimura M, Kawashima M, Inoue S, Mimura M, Tsubota K, Negishi K, Kishimoto T. The relationship of dry eye disease with depression and anxiety: a naturalistic observational study. Trans Vis Sci Tech. 2018;7(6): 35, https://doi.org/10.1167/ tvst.7.6.35.

  3. Labbe´ A, Wang YX, Jie Y, Baudouin C, Jonas JB, Xu L. Dry eye disease, dry eye symptoms and depression: the Beijing Eye Study. Br J Ophthalmol. 2013;97:1399–1403.

  4. Li M, Gong L, Sun X, Chapin WJ. Anxiety and depression in patients with dry eye syndrome. Curr Eye Res. 2011;36:1–7.

  5. Hallak JA, Tibrewal S, Jain S. Depressive symptoms in patients with dry eye disease: a case-control study using the beck depression inventory. Cornea. 2015;34:1545–1550.

  6. Kim KW, Han SB, Han ER, et al. Association between depression and dry eye disease in an elderly population. Invest Ophthalmol Vis Sci. 2011;52:7954–7958.

  7. Mrugacz M, Ostrowska L, Bryl A, Szulc A, Zelazowska-Rutkowska B, Mrugacz G. Proinflammatory cytokines associated with clinical severity of dry eye disease of patients with depression. Adv Med Sci. 2017;62:338–344.

  8. Ulusoy, M.O., Işık-Ulusoy, S. & Kıvanç, S.A. Evaluation of dry eye disease in newly diagnosed anxiety and depression patients using anterior segment optical coherence tomography. Eye and Vis 6, 25 (2019) doi:10.1186/s40662-019-0149-y. 

  9. Chhadva P, Lee T, Sarantopoulos CD, et al. Human tear serotonin levels correlate with symptoms and signs of dry eye. Ophthalmology. 2015;122:1675–1680.

  10. Sharif NA, Senchyna M. Serotonin receptor subtype mRNA expression in human ocular tissues, determined by RT-PCR. Mol Vis. 2006;12:1040–7.

  11. Chhadva P, Lee T, Sarantopoulos CD, Hackam AS, McClellan AL, Felix ER, et al. Human tear serotonin levels correlate with symptoms and signs of dry eye. Ophthalmology. 2015;122(8):1675–80.

  12. Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S. Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol. 2011;129:981–986.

  13. Ohayon MM, Schatzberg AF. Using chronic pain to predict depressive morbidity in the general population. Arch Gen Psyhiatry. 2003;60(1):39–47.

  14. Croft PR, Papergeorgiou AC, Ferry S, Thomas E, Jayson MI, Silman AJ. Psychologic distress and low back pain: evidence from a prospective study in the general population. Spine (Phila Pa 1976). 1995;20(24):2731–7.

  15. Alderson SL, Foy R, Glidewell L, McLintock K, House A. How patients understand depression associated with chronic physical disease – a systematic review. BMC Fam Pract. 2012;13:41.

  16. Kang H-J, Kim S-Y, Bae K-Y, et al. Comorbidity of depression with physical disorders: research and clinical implications. Chonnam Med J. 2015; 51:8–18.

  17. Kawashima M, Uchino M, Yokoi N, et al. Associations between subjective happiness and dry eye disease: a new perspective from the Osaka study. PLoS One. 2015;10:1–11.

 

Tracy Swartz
Consultative Optometrist Laser Eye Center in Huntsville & Decatur, AL specializing in anterior segment. President, Optometric Corneal, Cataract, and Refractive Society (OCCRS)

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