Jade Coats, OD

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Systemic disease and autoimmune conditions are frequently associated with an increased risk of dry eye syndrome. These patients are often affected by a combination of both evaporative and aqueous deficient dry eye; therefore, cognizance of a patient’s entire health history can help lead ODs to the root cause of chronic DES. Click on the following link to read more: 

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Dry Eye Patient (A) 

Dry Eye Patient (B) 

 (DES), but less than 1 million are actually receiving treatment.

 can sometimes be difficult because the condition is often multifactorial with several contributing factors leading to intermittent blur, fluctuations in vision, and stinging or watery eyes.

Related: Dry eye signs may signal risk for diabetic foot ulcers

Common systemic and autoimmune diseases have been found to be associated with an increased risk of dry eye disease; therefore, it is especially important to be familiar with these systemic conditions that contribute to aqueous deficiency and/or evaporative dry eye disease.

Dry eye disease is known to be multifactorial, with inflammation being a key contributing factor to the vicious dry eye cycle.

 Most commonly, evaporative dry eye causes tear hyperosmolarity which destroys the ocular surface cells. This damage causes an inflammatory response, leading to chronic dysfunction of the tear secretion, further increasing the tear osmolarity. In contrast, aqueous deficient dry eye involves inflammation attacking and damaging the lacrimal glands causing a decrease in tear production. 

*Important to note: Although the prevalence of DES is more common in women and may increase with age, dry eye symptoms affects people of all ages.

Click here to see a dry eye video related to this article (video A)

Click here to see a dry eye video related to this article (video B)

Related: Blood-derived serum tears go beyond conventional therapy

The Centers for Disease Control (CDC) reports more than 30 million Americans, or approximately 10 percent of the United States’ (U.S.) population, has 

 (DM), with another 7.2 million likely undiagnosed.

Both type 1 and type 2 diabetes affect the way the body regulates glucose, and it has been documented that the incidence of dry eye is correlated with increased levels of glycated hemoglobin (HbA1c).

The Beaver Dam Eye Study identifies diabetes as one of the leading systemic risk factors for dry eye with nearly 20 percent of participants between ages 43 and 86 exhibiting dry eye symptoms.

 In another study, insulin dependent diabetics demonstrated significantly decreased reflex tearing and increased conjunctival surface disease.

For patients with DM, it is important to remember that the decline in tear film function has been shown to be more severe in patients with advanced diabetic retinopathy

. Knowing this, it is important to recognize dry eye disease and its role in overall visual function for patients with 

Related: How to incorporate nutrition into dry eye practice

Autoimmune disease: Rheumatoid arthritis (RA), Lupus, and SjÃ¶gren’s syndrome (SS).

Rheumatoid arthritis is characterized as a chronic autoimmune disease that primarily targets the synovial tissues, damaging the joints of the body. Research has shown that chronic systemic inflammation has been identified as causing eye complications such keratoconjunctivitis sicca in up to 70 percent of RA patients.

 Interestingly, in that same study, only 12 percent of patients were currently being treated for ocular surface disease.

Related: Surgical update 2019: What every OD needs to know

Systemic lupus erythematous (SLE) is another chronic autoimmune disease that causes inflammation of various organs including skin, heart, joints, blood vessels, liver, kidney, and the eyes. It is thought that a higher concentration of cytokines and inflammatory markers in the tears of SLE patients may cause aqueous deficient dry eye disease. The prevalence of keratoconjunctivitis sicca symptoms in SLE has also been reported between 28 and 36 percent.

(SS) is a chronic autoimmune disease that attacks exocrine glands such as the salivary and lacrimal glands.

 With likely many people undiagnosed, SS affects nearly 4 million Americans with 10 percent of SS patients suffering from significant aqueous deficient 

With pharmaceutical options including Restasis (0.05% cyclosporine, Allergan), Cequa (0.09% cyclosporin, Sun Pharmaceutical), and Xiidra (5% lifitegrast, Novartis), optometrists now have multiple options to treat the signs and symptoms of dry eye disease by decreasing the inflammatory response and breaking down the dry eye cycle.

Related: Offer IPL as a treatment for MGD and dry eye disease

Thyroid-related disorders: Grave’s disease, Hashimoto’s thyroiditis

Thyroid disease has been shown to be associated with increased risk of dry eye, suggesting that hormone dysfunction may play a role in early onset of symptoms.

 Both Grave’s disease (hyperthyroidism) and Hashimoto’s disease (hypothyroidism) are associated with an abnormal production of thyroid hormone and can cause a combination of both aqueous deficient and evaporative dry eye disease.

Related: Recognize signs and treatment for patients with persistent PSP

Nearly 50 percent of patients affected by Graves’ disease suffer from thyroid-associated ophthalmopathy (TAO), a progressive eye disorder that is linked to an inflammatory response of the orbital tissues. TAO ranges from no signs or symptoms to severe vision loss, and may also be characterized by lagophthalmos, exophthalmos, restrictive myopathy, proptosis, and diplopia. Most commonly, a classic presentation of eyelid retraction and proptosis occurs in in 80 to 90 percent of patients with Graves’ disease.

Similarly with Hashimoto’s thyroiditis, proptosis is found to be a risk factor supporting previous research that found an increased palpebral fissure width might lead to ocular surface drying and tear film hyperosmolarity.

 Due to the increased ocular surface exposure caused by proptosis and eyelid retraction, a lubricating ointment at night can be recommended for overnight use to ensure proper eyelid seal.

Sleep disorder: Obstructive sleep apnea (OSA)

Obstructive sleep apnea affects more than 18 million Americans and is a life-threatening 

 causing decreased blood oxygen levels. With nearly one in four men and one in 10 women affected by interrupted breathing during sleep, it is important to identify undiagnosed patients who may exhibit other ocular manifestations of sleep apnea.

Related: New guidelines in OSD evaluation before surgery

In addition to evaporative dry eye symptoms, one prospective study of sleep apnea patients referred for a sleep study found that over 25 percent increasing to 40 percent among those with severe sleep apnea, also suffered from floppy eyelid syndrome.

The common treatment option for sleep apnea includes the use of a continuous positional airway pressure (CPAP). Nighttime ointment can be helpful for OSA patients to ensure that the eyes are protected and lubricated, even if a mask leak exposes the cornea to constant air.

Patients with allergies and asthma have been reported to have a higher incidence of dry eye disease. It is important to note that many patients suffering from allergic co-morbidities may be treating their symptoms with an over-the-counter oral or topical antihistamine, unaware that it could be contributing to their DED. Medications such as antihistamines, leukotriene receptor antagonists, and inhaled corticosteroids used in the treatment of asthma and allergies have been shown to exhibit adverse effects such as tear film dysfunction.

Related: Why OAB should be considered before cataract removal

Research has also indicated an association of risk factors for dry eye disease in patients with other systemic disease such as osteoporosis, migraine headaches, and 

In conclusion, systemic disease and autoimmune conditions are frequently associated with an increased risk of dry eye syndrome. These patients are often affected by a combination of both evaporative and aqueous deficient dry eye; therefore, cognizance of a patient’s entire health history can help lead ODs to the root cause of chronic DES.
	
	Asking a few extra questions during an eye exam regarding the status of a patient’s systemic conditions, and educating about their risk for dry eye, has been helpful in combating this disease by setting up realistic expectations of a treatment plan to control and maintain comfort.

More by Dr. Coats: Minimize symptoms of dry eye disease in refractive surgery patients

1. Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014;157(4): 799–806.

2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept. of Health and Human Services; 2017.

3. Yu L, Chen X, Qin G, Xie H, Lv P. Tear Film function in type 2 diabetic patients with retinopathy. Ophthalmologica. 2008;222(4):284-91.

4. Goebbels M. Tear secretion and tear film function in insulin dependent diabetics. Br J Ophthalmol. 2000;84(1):19–21.

5. Piper H, Douglas KM, Treharne GJ, Mitton DL, Haider S, Kitas GD. Prevalence and predictors of ocular manifestations of RA: is there a need for routine screening? Musculoskeletal Care. 2007 Jun;5(2):102-17.

6. Resch MD, Marsovszky L, NÃ©meth J, Bocskai M, KovÃ¡cs L, Balog A. Dry eye and corneal langerhans cells in systemic lupus erythematosus. J Ophthalmol. 2015;2015:543835.

7. Coursey TG, de Paiva CS. Managing SjÃ¶gren's Syndrome and non-SjÃ¶gren Syndrome dry eye with anti-inflammatory therapy. Clin Ophthalmol. 2014 Aug 4;8:1447–58.

8. Selter JH, Gire AI, Sikder S. The relationship between Graves' ophthalmopathy and dry eye syndrome. Clin Ophthalmol. 2014 Dec 31;9:57–62.

9. Santos M, Hofmann RJ. Ocular Manifestations of Obstructive Sleep Apnea. J Clin Sleep Med. 2017;13(11):1345–1348.

10. Bielory L. Ocular toxicity of systemic asthma and allergy treatments. Curr Allergy Asthma Rep. 2006 Jul;6(4):299-305.
	 

Articles

Common systemic conditions associated with dry eye disease

Laser refractive procedures such as laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) are  considered some of the most ground-breaking inventions in elective eye surgery.  

As a post-PRK patient and OD who manages pre- and postop visits for a large OD/MD practice specializing in refractive surgery, I have seen firsthand the benefits of being able to wake up on any given day and just see.


	I have found that the best way to combat postoperative dry eye is to know about it pre-operatively. Many patients seek refractive surgery due to the inability to tolerate contact lenses, and it is thought that the prevalence of patients already suffering from dry eye symptoms prior to refractive surgery ranges from 38 percent to 75 percent of patients.

Taking the time to explain to each patient exactly why it is necessary that their corneas be “primed and prepped” before surgery is an important step in the pre-op process. Forgoing aggressive treatment of dry eye disease (DED) and ocular surface irregularities may cause surgery to be delayed, or worse, the end results may not be as precise as they could have been.

Although there is no way to predict post-refractive dryness for an individual patient, pre-existing dry eye disease is a known risk factor for ocular surface problems after refractive surgery.

Postoperatively, up to 95 percent of patients experience symptoms of dry eye at some point over the first three months after surgery, which often improves with time.

The quicker optometric physicians can identify the cause of a patient’s subjective complaints, the faster patient satisfaction can be improved and the need for surgical enhancements minimized.

Before referring a patient for surgery or a refractive enhancement, ask: Has everything been done in order to solve the all ocular surface concerns? 

To help triage a post-refractive surgery patient who is seeing well-but who may be symptomatic with “blur,” “glare,” or “halos”-assess the following before referring for an enhancement.

Related: diving into dry eye can help physicians solve patients' woes


	Eyecare providers can dive deeper into investigating symptoms of DED by first looking at the eyelid function. Assessing the eyelid margins and blink status, as well as investigating the meibomian gland (MG) function and tear quality, can help to grasp the severity of DED. 

In patients having trouble with dry eye symptoms, observing the eyelids often reveals incomplete blinks and/or MG dysfunction and dropout. Spending a few extra minutes with these patients to help educate them about their dry eye condition has shown to be beneficial to patients and their overall satisfaction with surgical outcomes.

For symptomatic post-refractive dry eye patients, I often recommend preservative-free artificial tear lubrication such as Refresh Mega-3 (Allergan), which fortifies the lipid layer and helps to prevent tear evaporation.

Systane Complete (Alcon) is another option known for its nano-droplet technology, which may help target all three layers of the tear film to hydrate and add tear evaporation protection.

Other options to improve MG function include TearCare (Sight Sciences) and LipiFlow (Johnson & Johnson Vision)-devices that apply heat to the meibomian glands so the glands can be more easily expressed, thus helping to increase tear break-up time (TBUT) and reduce dry eye symptoms.


	I often see post-refractive patients also affected by common environmental factors that cause intermittent blur, glare, and symptoms of DED.

Whether due to a continuous positive airway pressure (CPAP) machine, living in a high-altitude area with low humidity, extended computer use, riding in an arid airplane, poorly placed vents at home/work-all of which cause dry eyes-it is important to identify and treat these likely culprits of chronic environmental dryness.

In addition to artificial tears, punctal plugs can also be inserted bilaterally to delay tear drainage and improve the amount of time tears stay on the ocular surface.

Other dry eye treatment for post-refractive surgery patients include Xiidra (lifitegrast, Novartis) to improve DED signs and symptoms and Restasis (cyclosporin, Allergan), an immunomodulator to help increase tear production. Note that Cequa (cyclosporin, Sun Pharma) is hitting the market as well.

Related: Managing dry eye key to patient satisfaction after cataract, refractive surgeries


	A patient with a larger pupil size can experience increased higher-order aberrations; thus, an increase in the blur and glare symptoms observed by the patient. Large pupils paired with ocular surface irregularities can have an even greater influence on the overall quality of vision perceived by the patient.

To help minimize this glare, I recommend OTC Lumify (brimonidine tartrate ophthalmic solution 0.025%, Bausch + Lomb) for its secondary off-label effect of diluted brimonidine. Just like other selective alpha-2 agonists, Lumify reduces redness by constricting the conjunctival venules (instead of arterioles like tetrahydrozoline, Visine). The use of brimonidine has been shown in office to have a small, yet often symptomatically positive effect on pupil size in scotopic conditions, which seems to help decrease the glare and halo effects of night driving. 


	To most effectively maximize results and minimize enhancements rates, treating any hint of dryness before surgery helps “prime and prep” the cornea for the best visual and surgical outcome.

Dry eyes can significantly affect patients’ perception of their surgical outcomes and level of satisfaction; therefore, continuing to treat DED before and after refractive surgery sets up the patient for success.

Whether choosing artificial tears, punctal plugs, TearCare, LipiFlow, Xiidra, or Restasis to treat DED in post-refractive surgery patients, the root of the dryness should be established and discussed with the patient early in the process.  

By making the patient aware of any dry eye and ocular surface problems-and taking the time to explain the realistic expectations of possible dry eyes in the future-it is easier for the patient to understand how to easily combat intermittent symptoms. 

Assessing the overall eyelid and tear function, inferior corneal staining, and pupil size as factors that could be playing a role in overall quality of vision after surgery can help tailor a dry eye treatment regimen.

Prior to referring for LASIK/PRK or a refractive enhancement, it is ideal to identify and aggressively treat underlying dry eye and OSD.


	1. Cohen E, Spierer O. Dry Eye Post-Laser-Assisted In Situ Keratomileusis: Major Review and Latest Updates. J Ophthalmol. 2018 Jan 28;2018:4903831.
	2. Yu EY, Leung A, Rao S, Lam DS. Effect of laser in situ keratomileusis on tear stability. Ophthalmology. 2000 Dec;107(12):2131-5.
	3. Solomon R, Donnenfeld ED, Perry HD. The effects of LASIK on the ocular surface. Ocul Surf. 2004 Jan;2(1):34-44.
	4. Edwards JD, Burka JM, Bower KS. Effect of brimonidine tartrate 0.15% on night-vision difficulty and contrast testing after refractive surgery. 2008 Sep;34(9):1538-41.

Author | Jade Coats, OD

Articles

Dry Eye Patient (A)

Dry Eye Patient (B)

Common systemic conditions associated with dry eye disease

Minimize symptoms of dry eye disease in refractive surgery patients