dry eye

Looking Beyond the Surface

Be aware of the numerous systemic diseases that manifest as dry eye syndrome.

Ernie Bowling, O.D., M.S.
Gadsden, Ala.

Patients presenting with dry eye syndrome (DES) are commonplace in an optometric practice. We all have these patients in our office and are comfortable with recognizing and managing the disease, yet sometimes these cases do not respond as rapidly — or in the manner we'd like — to the treatments we prescribe. Many unresponsive cases of DES are caused by an underlying systemic condition, and until that systemic condition is controlled, the disease will not respond to treatment as we'd expect.

There are a number of systemic diseases that can lead to DES. Although some individuals have true ocular surface disease alone, numerous systemic diseases include an ocular component that manifests as DES (keratoconjunctivitis sicca). Therefore, it's crucial we identify any systemic cause of the ocular surface disease, as doing so can aid us in DES management.

The most common associations between systemic diseases and DES are autoimmune disorders, predominantly Sjögren's syndrome and rheumatoid arthritis.^1-3 Other autoimmune disorders that can cause DES include lupus erythematosus, scleroderma, thyroiditis and graft-vs.-host disease.^3,4 Skin disorders, such as rosacea, are also likely to have a dry eye component (e.g., evaporative dry eye or meibomian gland dysfunction).^5,6

A variety of other systemic diseases, including diabetes, Raynaud's syndrome, HIV/AIDS, multiple sclerosis, giant cell arteritis and Graves' disease, also manifest with ocular symptoms, but these diseases are much more likely to have been diagnosed before the ocular symptoms present. Lastly, some systemic medications, such as antihypertensives, can adversely affect the tear film and lead to DES.

Autoimmune disorders

Autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus and thyroid disease place the ocular surface at risk for DES.

► Rheumatoid arthritis (RA). RA is a chronic inflammatory disease that affects approximately 2% of the U.S. population older than age 60.⁷ More than 90% of people who have RA have DES, with 50% presenting with moderate-to-severe forms of DES.⁸ Up to 31% of patients who have RA have a dry eye component and co-existing Sjögren's syndrome.⁸

► Sjögren's syndrome. Sjögren's syndrome is a clinical condition of aqueous tear deficiency combined with dry mouth. Sjögren's syndrome is one of the most prevalent autoimmune disorders affecting upwards of four million Americans.⁹ Nine out of 10 patients affected are women. The syndrome is classified as primary — patients without a defined connective tissue disease — and secondary — patients who have a confirmed connective tissue disease (See “Practice Rheumoptometry,” in this issue.)

► Systemic lupus erythematosus (SLE). (SLE) is a chronic, autoimmune, multisystem disease, which may affect the eyes and/or visual system. DES is the most common ocular feature of SLE and is often associated with secondary Sjögren's syndrome.¹⁰ Roughly 20% of patients who have SLE have secondary Sjögren's syndrome.¹¹ Usually, symptoms are relatively mild (irritation, redness) but severe pain and visual loss may occur.

Other ocular manifestations of SLE include recurrent corneal erosions and punctate epithelial loss.¹² In some cases, ocular surface disease may indicate a reactivation of SLE that was thought to be in remission.¹³

► Thyroid eye disease (TED). TED is an autoimmune orbital reaction, which typically manifests in middle age. TED is a common systemic disease associated with dry eye due to thyroid hormone imbalance and exophthalmos-related corneal exposure.¹⁴ Early symptoms include foreign body sensation, DES-caused excessive tearing, conjunctival or eyelid redness and swelling, blurred vision and retro-orbital pain. Occult TED is a potential cause of inflammatory ocular surface disease with dry eye symptomatology and should be considered in the differential diagnosis when evaluating DES patients.¹⁵

Inflammatory conditions

Several inflammatory conditions, including irritable bowel syndrome and Crohn's disease have a high incidence of DES. In one study, 42% of patients who had inflammatory bowel disease had DES.¹⁶

Diabetes

Diabetes is already one of the most common metabolic diseases on the planet, and the incidence of type 2 diabetes is expected to grow exponentially in the immediate future. One of the most common ocular manifestations of diabetes is DES.¹⁷ More than half of patients who have diabetes experience dry eye symptoms (54.3% in one study), such as burning, foreign body sensation and ocular dryness.¹⁸ Potential explanations include chronic tear secretion deficiency, peripheral neuropathy and hyperglycemia, which leads to corneal epitheliopathy-producing complications. These complications: hyperosmolarity, punctate keratopathy, recurrent erosions, persistent epithelial defects, neurotrophic keratopathy, wound healing delay and a high risk of microbial keratitis.¹⁹ Tear proteins of diabetic patients are different from those of healthy subjects, and alterations in diabetic tears are correlated with the duration of the diabetic disease.²⁰ Reflex tearing has been demonstrated to be significantly decreased in insulin-dependent diabetics.²¹ In severe cases of diabetic neurotrophic keratopathy, patients may exhibit no symptoms or may seem to have a high tolerance for ocular surface dryness.¹⁹ This may be the direct result of the reduction in corneal sensation that people who have diabetes experience. As diabetes can also lead to neurotrophic keratitis, comanagement with an endocrinologist is highly recommended.

HIV/AIDS

DES occurs in 20% to almost 40% of HIV-positive hosts in the later stages of AIDS.²² Those afflicted are more susceptible to bacterial keratitis, and abnormalities in the composition of the tear film are typically present.²³ The ocular dryness is due to the combined effects of the HIV-mediated inflammatory destruction of primary and accessory lacrimal glands and to the direct conjunctival damage as a result of the HIV virus itself.²⁴ As many as 20% of people who have HIV/AIDS develop damaged lacrimal glands that lead to ocular dryness.²⁵

Systemic medications

Any systemic medication that dries the mucosal surface or slows the activity of the mucosal surface may produce DES. Additionally, if a medication causes dry mouth, it will also cause dry eye. The medications implicated in causing DES: antihypertensives, beta-blockers, cholesterol-lowering medications, anticoagulants/aspirin therapy (which may also aggravate the condition, as they are secreted in the tear film), genitourinary medications (e.g. hormone therapy, both estrogen and androgen), psychogenic medications (including those to treat panic disorder) and dermatology treatments (such as isotretinoin).^26-30 Almost 75% of patients who use glaucoma medications have some signs and symptoms of DES. This is a direct result of the preservatives in the formulations, the side effects of the active drugs and the overall age group typically affected by glaucoma. Also, instillation of eye medications (in general?), especially instilled frequently (e.g., more than q.i.d.), may prevent the normal maintenance of the tear film and cause dry eye symptoms.

Because systemic diseases and the drugs used to treat them can diminish the effectiveness of prescribed DES treatments, we must both determine the drugs patients are taking and in identify the possible presence of these diseases. Armed with this data, we are better equiped to provide DES symptom relief. OM

1. Takei S. Sjögren's syndrome (SS) in childhood: is it essentially different from adult SS (in Japanese). Nihon Rinsho Meneki Gakkai Kaishi. 2010; 33(1): 8-14.
2. Pinheiro MN Jr., dos Santos PM, dos Santos RC, et al. Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren's syndrome patients (in Portuguese). Arq Bras Oftalmol. 2007; Jul-Aug 70(4): 649-55.
3. Ostanek L, Modrzejewska M, Bobrowska-Snarska D, Brzosko M. Ocular manifestations in patients with systemic lupus erythematosus and antiphospholipid syndrome (in Polish). Pol Arch Med Wewn 2007; 117 suppl:18-23.
4. Viso E, Rodriguez-Ares MT, Gude F. Prevalence of and associated factors for dry eye in a Spanish adult population (the Salnes Eye Study). Ophthalmic Epidemiol. 2009 Jan-Feb; 16(1):15-21.
5. Djakovic Z, Milenkovic S, Pesko P, et al. Rosacea as a multisystemic disease (in Serbian). Srp Arh Celok Lek. 2003 Nov-Dec;131(11-12): 474-8.
6. Patel SJ, Lundy DC. Ocular manifestations of autoimmune disease. Am Fam Physician 2002 Sep 15; 66(6): 991-8.
7. Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003 Apr; 48(4): 917-26.
8. Fujita M, Igarashi T, Kurai T, et al. Correlation between dry eye and rheumatoid arthritis activity. Am J Ophthalmol 2005 Nov; 140(5):808-813.
9. Sjögren's Syndrome Foundation. About Sjögren's Syndrome. www.sjogrens.org/home/about-sjogrens-syndrome. (Accessed September 3, 2011.)
10. Read RW. Clinical mini-review: systemic lupus erythematosus and the eye. Ocul Immunol Inflamm. 2004 Jun; 12: 87–99.
11. Scofield RH, Bruner GR, Harley JB, et al. Autoimmune thyroid disease is associated with a diagnosis of secondary Sjögren's syndrome in familial systemic lupus. Ann Rheum Dis. 2007 Mar;66(3): 410–3.
12. Sivaraj RR, Durrani OM, Dennis-ton AK, et al. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford) 2007 Dec; 46(12):1757-62.
13. Nguyen QD, Foster CS. Systemic lupus erythematosus and the eye. Int Ophthalmol Clin. 1998 Winter;38: 33-60.
14. Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older population. Optom Vis Sci. 2008 Aug; 85(8): 668-74.
15. Gupta A, Sadeghi PB, Akpek EK. Occult thyroid eye disease in patients presenting with dry eye symptoms. Am J Ophthalmol. 2009 May;147(5):919-23.
16. Cury DB, Moss AC. Ocular manifestations in a community-based cohort of patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010 Aug; 16(8):1393-96.
17. Dall TM, Zhang Y, Chen YJ, et al. The economic burden of diabetes. Health Aff (Millwood). 2010 Feb; 29(2):297-303.
18. Manaviat MR, Rashidi M, Afkhami-Ardekani M, Shoja MR. Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC Ophthalmol. 2008 Jun 2; 8:10.
19. Alves Mde C, Carvalheira JB, Módulo CM, Rocha M. Tear film and ocular surface changes in diabetes mellitus (in Portuguese). Arq Bras Oftalmol. 2008 Nov-Dec; 71(6 suppl): 96-103.
20. Grus FH, Sabuncuo P, Dick HB, et al. Changes in the tear proteins of diabetic patients. BMC Ophthalmol. 2002 Oct 31; 2:4.
21. Goebbels M. Tear secretion and tear film function in insulin dependent diabetics. Br J Ophthalmol. 2000 Jan; 84 (1):19-21.
22. Adnexal and anterior segment manifestations of HIV/AIDS. Int Ophthalmol Clin. 2007 Spring; 47(2):15–32.
23. Matui R, Nussenblatt R, de Smet MD. Prevalence of tear hyposecretion and vitamin A deficiency in patients with AIDS. Invest Ophthalmol Vis Sci 1994; 35: 1308.
24. Ormerod LD, Dailey JP. Ocular manifestations of cat-scratch disease. Curr Opin Ophthalmol. 1999 Jun; 10(3): 209–16.
25. Beyda N, Cluck D, Taba KE, et al. Ocular manifestations of systemic diseases. US Pharm 2010; 35 (4): HS-2-HS-8.
26. Petounis AD, Akritopoulos P. Influence of topical and systemic beta-block-ers on tear production. Int Ophthalmol. 1989 Jan; 13(1-2):75-80.
27. Fraunfelder FW. Ocular hemorrhage possibly the result of HMG-CoA reductase inhibitors. J Ocul Pharmacol Ther. 2004 Apr; 20(2):179-82.
28. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Arch Ophthalmol. 2009; 127(6):763-68.
29. Lutz EG. Allergic conjunctivitis due to diazepam. Am J Psychiatry. 1975; 132(5):548.
30. Fraunfelder FT, LaBraico JM, Meyer SM. Adverse ocular reactions possibly associated with isotretinoin. Am J Ophthalmol 1985; 100(4): 534-37.

Dr. Bowling is in private practice in Gadsden, Ala. He writes and lectures extensively on several eyecare topics, including ocular allergy and dry eye. E-mail drbowling@windstream.net. Or, send comments to optometricmanage ment@gmail.com.