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When times aren’t “20/happy”

Optometry Times JournalJune digital edition 2021
Volume 13
Issue 6

Many systemic conditions have higher incidence with depression, anxiety

As primary eye care providers, optometrists may face unsettling situations in which a patient is exhibiting behavioral or mental health crisis while in the office. Interestingly, many of the systemic conditions ODs treat regularly have a higher incidence with mental conditions such as depression and anxiety.

Early recognition, referral, and treatment of common mental health conditions such as these can not only improve quality of life for patients but also help prevent complications of cooccurring behavioral health and medical comorbidities while reducing overall health care costs.1 Being familiar with the common systemic and ocular associations with mental illness along with being more aware of a patient’s behavioral health status may help to guide an OD to provide an appropriate mental health referral.

In the United States, the estimated lifetime risk of a major depressive episode approaches 30%. The incidence of suicide, which is associated with a diagnosis of depression more than 50% of the time, has been increasing and is the 10th-leading cause of death in the United States.2-4

Depression versus anxiety

While mental health focuses on a person’s psychological state, behavioral health is a broad umbrella that incorporates physical and mental struggles, including daily eating habits, exercise routines, and alcohol consumption. ODs are in a distinctive position to routinely assess these details reported by patients; therefore, it may behoove ODs to further educate themselves on how to identify mental conditions and refer when appropriate.

To properly identify someone who may need further mental health assistance, it is important to better understand the definitions and characteristics of depression and anxiety.


Clinical depression is a common condition, affecting more than 1 in 6 individuals at some point in their lives.5 While most encounter periods of sadness or grief during their lives, clinical depression is characterized by persistent, and nearly constant, states of these emotions. Signs and symptoms of clinical depression include any of the following being present for 2 or more weeks:6

Persistent sadness

Loss of interest in hobbies



Difficulty concentrating

Difficulty sleeping or getting out of bed

Changes in appetite

Suicidal ideations

The onset of major depressive disorder peaks with most patients presenting in their 20s, with a second peak of incidence of patients in the 50s.7 Women are twice as likely as men to be diagnosed with depression.8 Risk factors for major depressive disorder include divorce or separation, episodes of depression in the past, increased stress, a history of trauma, and a family history of depression in first-degree relatives.9 Depression can occur at any age, and as will be discussed later in this article, is often present with other systemic comorbidities. In fact, depression can exacerbate these problems.6


All individuals will experience anxiety in their lives as a response to stressful situations. With the ongoing COVID-19 pandemic, most individuals have likely experienced episodes of anxiety regarding concerns about their health and that of their families and how the pandemic might affect their work and livelihood. Although these anxious responses in short duration are normal, anxiety disorders hold a more chronic presence in the lives of those who experience them. These disorders fall under several categories according to the National Institute of Mental Health,10 including:

Generalized anxiety disorder (GAD): Excess anxiety on a near daily basis for at least 6 months. This persistent anxiety has a profound effect on daily activities and may manifest with symptoms such as extreme restlessness, loss of sleep, difficulty focusing, fatigue, and irritability.10

Panic disorder: Recurrent panic attacks that may be triggered by certain situations or be unexpected. These episodes may be accompanied by shortness of breath, shaking, sweating, heart palpitations, and feeling of impending doom.10

Phobia-related disorders: Fear of certain situations or things to the extent that other normal activities of daily living are affected.10

Although depression and anxiety represent 2 separate clinical entities, they frequently overlap. Approximately 85% of patients with depression experience anxiety, and 90% of patients with anxiety also exhibit signs of depression.11

Treatment options for each condition involve a combination of psychological (ie, clinical counseling) and pharmacologic therapies (antidepressants) depending on severity of condition. However, more than one-third of patients who experience these conditions seek treatment, and only half of those are offered helpful interventions.11

Systemic disease and mental health

There is evidence for an association between depression and anxiety with a multitude of systemic conditions such as diabetes, lung disease, arthritis, autoimmune disorders, heart disease, and cancer, to name a few.1,2 As ODs assess patients with these systemic conditions in their offices daily, they should consider screening patients to ensure they are receiving care.

Psychiatric conditions such as depression and anxiety have been linked to the following systemic conditions.


Patients with diabetes need regular diabetic retinopathy examinations as well as treatment for common findings in these patients such as dry eye, cataract, and glaucoma. The diabetes epidemic is well known and continues to grow, with a prevalence estimate of as many as 1 in 11 adults.12 Research shows that depression rates run higher by as many as 2 to 3 times in comparison to patients without diabetes, whereas anxiety is present in as many as 40% of these patients.12 While diabetes may cause or contribute to mental health concerns, evidence shows depression may be a contributing factor in the development of diabetes. Patients diagnosed with depression have a 60% increased risk of developing type 2 diabetes compared with control populations.13

Obstructive sleep apnea (OSA)

OSA is tied by causation or exacerbation to many systemic and eye related conditions, including diabetes and diabetic retinopathy, hypertension, glaucoma, floppy eyelid syndrome, and nonarteritic ischemic optic neuropathy.14 Because of the consistent interruption of normal sleep, which can lead to development of depression, it is not surprising that a bidirectional relationship exists between these 2 conditions with nearly 18% of patients experiencing one also experiencing the other.15

Autoimmune diseases

Autoimmune conditions can be burdensome,with varying intensity and flares that may lead to concern for short- and long-term complications. This may contribute to depression and anxiety in these patients. Correlations are seen in patients with lupus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroiditis, and multiple sclerosis, among others.16-18 Moreover, an increase in cytokine activation may be a contributing factor in the cause of depression, suggesting that inflammatory factors released in these conditions may be a primary contributing factor to depression.16

Heart disease

When hospitalized for a cardiac event, such as acute myocardial infarction or coronary artery bypass graft surgery, approximately 1 in 5 patients meets diagnostic criteria for depression and up to 1 in 3 experience severe anxiety.19 Because patients who are anxious or depressed after a cardiac event are at increased risk of a subsequent event and premature death,19 it is especially important to ensure that patients recently affected by heart disease are receiving proper mental health care.


Stroke is the third-leading cause of death globally, affecting 15 million individuals annually.20 Poststroke depression (PSD) has been reported in nearly 33% of stroke patients and is considered the most frequent and important neuropsychiatric consequence of a stroke that negatively affects recovery.20 PSD is characterized as a mood disorder with depressive features, major depressivelike episodes, manic features, or mixed features, which increases the disease deterioration, causes further social function defects, and increases the risk of suicide.20 Screening for mental illness in poststroke patients is important because adequate treatment eye-related conditions may be dependant on successful therapy for other comorbid conditions, such depression and anxiety secondary to stroke.20

Fibromyalgia and migraines

Fibromyalgia and depression share similar pathophysiology and are targeted by the same drugs with dual action on serotoninergic and noradrenergic systems.21 Fibromyalgia is considered an affective spectrum disorder. This category includes physical conditions such as migraines and psychiatric disorders such as21:

Attention-deficit/hyperactivity disorder

Bulimia nervosa

Dysthymic disorder

Generalized anxiety disorder

Major depressive disorder

Obsessive compulsive disorder

Panic disorder, posttraumatic stress disorder

Premenstrual dysphoric disorder

Social phobia


The mental health of individuals living with and surviving cancer is an important factor to consider as an OD. Although many factors such as the type and stage of cancer can affect the severity of mental illness, one meta analysis of several studies found that the estimated prevalence of depression varied across treatment settings. Depression ranged from 5% to 16% in outpatients, 4% to 14% in inpatients, 4% to 11% in mixed outpatient and inpatient samples, and 7% to 49% in palliative care.22

More research and a personalized approach to support the psychological health of individuals with cancer are needed, as well as proper referral for treatment of comorbid depression and anxiety.22

Ocular disease and mental health

In addition to considering systemic conditions when assessing a patient’s overall health status, it is also important to consider ocular surface disease, visual impairment from conditions such as age-related macular degeneration (AMD) and glaucoma, and chronic inflammatory disease such as uveitis. All these ocular diseases may further contribute to mental illness.2,4,23,24

An investigation into appropriate treatment strategies, beyond just the eye, may be an important indirect step in treating the overall ocular disease. In studies across the globe, patients suffering from certain ocular conditions have been shown to have an increased prevalence of depression and anxiety.2 The perception of visual impairment, rather than objective measures such as visual acuity, has been shown to be more strongly correlated with depression. Interestingly, patients who report functional vision problems, such as difficulty driving, navigating steps, or seeing objects in the peripherary, are 90% more likely to be depressed than patients who do not report these same problems, independent of visual acuity.2,24

Dry eye disease

Depression and anxiety may be a significant but underrecognized comorbidity in patients with chronic ocular inflammation such as dry eye disease (DED).2,4 One meta-analysis demonstrated that the prevalence of depression among DED patients was 25%, ranging upward of 57%.2 An increased frequency of dry eye in patients being treated for a variety of psychiatric illnesses, including depression and anxiety, has been observed in a large population-based study.2

It is thought that patients receiving treatment for DED would also benefit from treatment for depression and anxiety.2,4 Depression and anxiety symptoms may also affect other psychological systems.4,23 ODs should view DED among the same group of chronic systemic medical illnesses with implications for psychiatric disease and be more cognizant to psychiatric symptoms reported in patients with DED.

Note that the anticholinergic activity of some antidepressant medications has been identified as a risk factor for DED.2 Patients being treated for depression and or anxiety may need to be further screened for DED and vice versa.


AMD is a common cause of visual impairment and blindness that affects nearly 196 million individuals worldwide, which is approximately 9% of the global population.24 Depression and anxiety are more common in adults with visual impairment. Clinically significant subthreshold symptoms of depression are found in approximately one-third of older adults with AMD and impaired vision, which is nearly twice as high as the lifetime prevalence rates in the general older population.23,24

Visual impairment worsened by AMD is associated with increased functional disability and emotional stress, leading to an increased risk of mental health problems in patients with AMD. Compared with other eye diseases, the rate of depression in older adults with AMD was the highest at 39%.24 The rate of anxiety was variable, but the prevalence of anxiety among patients with AMD ranges from 9.6% to 30%.24 It is important to note that other mental conditions such as agoraphobia (4.2%) and social phobia (2.4%) were prevalent among those with visual impairment due to AMD.24

Although research has shown that behavioral interventions can treat or prevent depression in AMD,24 until an AMD-specific behavioral and self-management program model is available, traditional low vision rehab is considered the best treatment option ODs can provide, coupled with an appropriate referral for mental health care when necessary. Because AMD can affect functional and psychological well-being, ODs should educate AMD patients that symptoms of anxiety and depression can be alleviated by treatments such as medication from their medical providers, psychotherapy, and low vision rehabilitation.24


Glaucoma is a chronic, potentially blinding condition requiring lifelong treatment and regular follow-up visits. Although the condition varies in severity, the potential threat of irreversible vision loss can have a significant impact on patient psyche. As with chronic systemic disorders, correlation exists between the glaucoma and the presence of depression and anxiety.25

Research shows potential exacerbation of glaucoma by these afflictions. Results from one study showed significant association with anxiety or concomitant depression and anxiety and conversion from glaucoma suspect to the development of glaucoma.26 Results from another study showed patients with anxiety exhibited higher and more variable intraocular pressure (IOP), faster retinal nerve fiber layer progression, and increased presence of disc hemorrhage, postulating that continued emotional stress has a significant effect on the autonomic nervous system, which further affects IOP and blood flow.27 These study results indicate that the relationship between glaucoma and these mental health disorders may have 2-way interaction in affecting disease progression.


HLA-B27-associated uveitis (B27-AU) is another ocular condition in which research has found that patients with the condition had more depressive symptoms and negative coping strategies than patients in the control group. Perhaps implicating stress and life events as a trigger for relapses, results from this study demonstrated that female patients with B27-AU react with depression, and male patients use negative stress coping strategies. Some 57.9% of patients reported believing that psychological distress was a trigger for their relapses, and 34.5% stated specific life events triggered them.28

Although the prognosis of anterior uveitis is good, complications of HLA-B27-associated uveitis can include posterior synechiae, cataract, glaucoma and hypotony, although only less than 2% develop legal blindness andless than 5% have visual impairment.28 When a patient presents with recurrent anterior uveitis, ensure the patient seeks follow-up treatment with a rheumatologist so the underlying inflammatory cause can be treated.

How ODs can help

Especially during COVID-19, ODs may be the only health care professionals a patient has seen or will see for significantly more time compared to prepandemic. This induced isolation requires all health care providers to be more connected, and a team approach is needed to care for patients’ comprehensive health.

Although discussing depression and anxiety with patients during their eye examination may be awkward, uncomfortable, and time consuming, ODs are able to identify vision-related deficiency and psychiatric symptoms affected by ocular disease. ODs can play a role in destigmatizing mental illness by emphasizing that depression is common and an understandable reaction to vision loss.

All health care providers should watch for identifying signs of mental illness. Results from one study showed that 38% of individuals who attempted suicide visited a health care provider within the previous week.9 The coexistence of depression and anxiety is frequent with more than 50% of patients with depression also diagnosed with clinically significant anxiety.9 Coexistence of both conditions decreases the chance of success with standard treatments compared with patients who have depression without anxiety.9

Patient surveys are commonly used by ODs to screen patients for mental health diseases. Many are available, and all have pros and cons, focus, length, and intended use.9 The Patient Health Questionnaire (PHQ-4) has utility in eye care clinics because it is quick, simple, and accurate.8This 4-question, 12-point survey screens for depression and anxiety and can help facilitate consultation with primary care and other mental health specialists.8

When concerns about a patient’s mental well-being arise, a phone call to the patient’s primary care provider is recommended as the best next step. If the patient doesn’t have a relationship with a primary care physician or the situation seems emergent, it is recommended that ODs work with emergency department colleagues. In our experience, emergency department colleagues are happy to take over care in these situations. In addition, the National Suicide Prevention Lifeline is available 24 hours: 1-800-273-8255.

Although mental health conditions are best treated by primary care, psychology, and psychiatry colleagues, ODs play an integral role to get patients the help they need with an appropriate and timely referral. Because ODs sometimes spend more time with their patients due to systemic and ocular conditions requiring chronic care, an OD may be the patient’s most trusted and visited health care provider. Learning the details of systemic and ocular comorbidities associated with depression and anxiety is an important step in getting patients the care they need.


1. Zheng Y, Wu X, Lin X, Lin H. The prevalence of depression and depressive symptoms among eye disease patients: a systematic review and meta-analysis. Sci Rep. 2017;7:46453. doi:10.1038/srep46453

2. van der Vaart R, Weaver MA, Lefebvre C, Davis RM. The association between dry eye disease and depression and anxiety in a large population-based study. Am J Ophthalmol. 2015;159(3):470-474. doi:10.1016/j.ajo.2014.11.028

3. Wen W, Wu Y, Chen Y, et al. Dry eye disease in patients with depressive and anxiety disorders in Shanghai. Cornea. 2012;31(6):686-692. doi:10.1097/ICO.0b013e3182261590

4. Kitazawa M, Sakamoto C, Yoshimura M, et al. The relationship of dry eye disease with depression and anxiety: a naturalistic observational study. Transl Vis Sci Technol. 2018;7(6):35. doi:10.1167/tvst.7.6.35

5. What is depression? American Psychiatric Association. October 2020. Accessed May 13, 2021. https://www.psychiatry.org/patients-families/depression/what-is-depression

6. Depression. National Institute of Mental Health. Updated February 2018. Accessed May 13, 2021. https://www.nimh.nih.gov/health/topics/depression/index.shtml

7. Anxiety disorders. National Institute of Mental Health. Updated July 2018. Accessed May 13, 2021. https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml

8. Tiller JW. Depression and anxiety. Med J Aust. 2013;199(S6):S28-S31. doi:10.5694/mja12.10628

9. Bădescu SV, Tătaru C, Kobylinska L, et al. The association between diabetes mellitus and depression. J Med Life. 2016;9(2):120-125.

10. Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care. 2008;31(12):2383-90. doi:10.2337/dc08-0985

11. West SD, Turnbull C. Obstructive sleep apnoea. Eye (Lond). 2018;32(5):889-903. doi:10.1038/s41433-017-0006-y

12. Jehan S, Auguste E, Pandi-Perumal SR, et al. Depression, obstructive sleep apnea and psychosocial health. Sleep Med Disord. 2017;1(3):00012.

13. Pryce CR, Fontana A. Depression in autoimmune diseases. Curr Top Behav Neurosci. 2017;31:139-154. doi:10.1007/7854_2016_7

14. Siegmann EM, Müller HHO, Luecke C, Philipsen A, Kornhuber J, Grömer TW. Association of depression and anxiety disorders with autoimmune thyroiditis: a systematic review and meta-analysis [published correction appears in JAMA Psychiatry. 2019;76(8):872. doi:10.1001/jamapsychiatry.2019.1643]. JAMA Psychiatry. 2018;75(6):577-584. doi:10.1001/jamapsychiatry.2018.0190

15. Boeschoten RE, Braamse AMJ, Beekman ATF. Prevalence of depression and anxiety in multiple sclerosis: a systematic review and meta-analysis. J Neurol Sci. 2017;372:331-341. doi:10.1016/j.jns.2016.11.067

16. Murphy B, Le Grande M, Alvarenga M, Worcester M, Jackson A. Anxiety and depression after a cardiac event: prevalence and predictors. Front Psychol. 2020;10:3010. doi:10.3389/fpsyg.2019.03010

17. Shi Y, Yang D, Zeng Y, Wu W. Risk factors for post-stroke depression: a meta-analysis. Front Aging Neurosci. 2017;9:218. doi:10.3389/fnagi.2017.00218

18. Gracely RH, Ceko M, Bushnell MC. Fibromyalgia and depression. Pain Res Treat. 2012;2012:486590. doi:10.1155/2012/486590

19. Niedzwiedz CL, Knifton L, Robb KA, Katikireddi SV, Smith DJ. Depression and anxiety among people living with and beyond cancer: a growing clinical and research priority. BMC Cancer. 2019;19(1):943. doi:10.1186/s12885-019-6181-4

20. 2. van der Vaart R, Weaver MA, Lefebvre C, Davis RM. The association between dry eye disease and depression and anxiety in a large population-based study. Am J Ophthalmol. 2015;159(3):470-474. doi:10.1016/j.ajo.2014.11.028

21. 4. Kitazawa M, Sakamoto C, Yoshimura M, et al. The relationship of dry eye disease with depression and anxiety: a naturalistic observational study. Transl Vis Sci Technol. 2018;7(6):35. doi:10.1167/tvst.7.6.35

22. Cimarolli VR, Casten RJ, Rovner BW, Heyl V, Sörensen S, Horowitz A. Anxiety and depression in patients with advanced macular degeneration: current perspectives. Clin Ophthalmol. 2015;10:55-63. doi:10.2147/OPTH.S80489

23. Brody BL, Gamst AC, Williams RA, et al. Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration. Ophthalmology. 2001;108(10):1893-1900; discussion 1900-1901. doi:10.1016/s0161-6420(01)00754-0

24. Zhang X, Olson DJ, Le P, Lin FC, Fleischman D, Davis RM. The association between glaucoma, anxiety, and depression in a large population. Am J Ophthalmol. 2017;183:37-41. doi:10.1016/j.ajo.2017.07.021

25. Berchuck S, Jammal A, Mukherjee S, Somers T, Medeiros FA. Impact of anxiety and depression on progression to glaucoma among glaucoma suspects. Br J Ophthalmol. Published online August 29, 2020.

26. Shin DY, Jung KI, Park HYL, Park CK. The effect of anxiety and depression on progression of glaucoma. Sci Rep. 2021;11(1):1769. doi:10.1038/s41598-021-81512-0

27. Maca SM, Schiesser AW, Sobala A, et al. Distress, depression and coping in HLA-B27-associated anterior uveitis with focus on gender differences. Br J Ophthalmol. 2011;95(5):699-704. doi:10.1136/bjo.2009.174839

28. Mulvaney-Day N, Marshall T, Piscopo KD, et al. Screening for behavioral health conditions in primary care settings: a systematic review of the literature. J Gen Intern Med. 2018;33(3):335-346. doi:10.1007/s11606-017-4181-0

29. Kroenke K, Spitzer RL, Williams JBW, Löwe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009;50(6):613-621. doi:10.1176/appi.psy.50.6.613

30. Burke KC, Burke JD Jr, Regier DA, Rae DS. Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry. 1990;47(6):511518. doi:10.1001/archpsyc.1990.01810180011002

31. 29. Kroenke K, Spitzer RL, Williams JB, Löwe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009 Nov-Dec;50(6):613-21. doi: 10.1176/appi.psy.50.6.613.

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