11th Annual Dry Eye Report
Recalibrate Dry Eye Management

The tear film is in a state of delicate balance. Likewise, we must carefully balance a dry eye patient’s risk factors, symptoms and clinical tests to determine an effective treatment strategy.

By Mile Brujic, O.D.

Goal Statement:

Dry eye disease is one of the most common conditions that primary eye care providers encounter. However, it is often difficult to identify dry eye because of a lack of consistent disease identification criteria. In an effort to help clinicians detect and combat this prevalent occular condition, this paper provides essential information on current diagnostic testing and offers successful treatment strategies for dry eye management.

Faculty/Editorial Board:

Mile Brujic, O.D.

Credit Statement:

This course is qualified for 2 hours of CE Credit. COPE ID: 27365-AS. Check with your local state licensing board to see if this counts toward your CE requirement for relicensure.

Joint-Sponsorship Statement:

This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.

Disclosure Statement:

Dr. Brujic has no relationships to disclose.

---

Dry eye disease is perhaps the most common condition that primary eye care providers encounter in daily practice. The overall prevalence of dry eye varies anywhere from 3.5% to 33% across different patient populations.^1-5 However, it is often difficult to identify dry eye because of a lack of consistent disease identification criteria.

In 2007, members of the International Dry Eye WorkShop (DEWS) published a consensus regarding the fundamental aspects of dry eye disease. The DEWS group defined dry eye 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.”⁶

This definition encompasses many factors that are critical to consider when identifying and treating patients with dry eye. The tear film is an intricate entity that balances the structural integrity of the mucin, aqueous and lipid layers. Additionally, the status of the cornea, conjunctiva and lid margins is integral to identifying and treating our dry eye population.⁷ This paper details current diagnostic testing and successful treatment strategies for dry eye management.

Risk Factors

Many factors pose a threat to the normal function of the ocular surface. Some of the most common risk factors of dry eye are:

• Medications. Common systemic medications, including antihistamines, angiotensin-converting enzyme (ACE) inhibitors, decongestants, diuretics, anti-depressants, oral contraceptives and isotretinoin, can exacerbate dry eye symptoms.⁸

• Climate. Low humidity can worsen symptoms in patients with existing symptoms and may exacerbate symptoms in asymptomatic individuals with a marginal tear film. Also, upwardly-directed forced air vents may compromise a patient’s tear film.

• Extensive visual tasking. Working at video display terminals strains the integrity of the tear film. In one study, dry eye patients working in front of a computer monitor had an average spontaneous eye blink rate of less than half of the rate of dry eye patients engaged in conversation (6.6 blinks/min vs. 16.8 blinks/min).⁹

• Aging. Aging increases a patient’s risk for dry eye development.⁵ For example, hormonal changes in menopausal and postmenopausal women challenges tear film integrity.¹⁰ Additionally, women on hormone replacement therapy have an increased risk of developing dry eye syndrome.¹¹ This finding has been supported by a rabbit model that indicated estrogen increased the expression of matrix-metalloproteinases (MMPs) -2 and -9 from the lacrimal gland.¹² Excessive levels of MMPs are pro-inflammatory and have been shown to slow reepithelialization.

• Nutrition. Recent research suggests that nutrition may play a significant role in ocular surface health. One study employed a food validation frequency questionnaire to examine a crosssection of more than 30,000 female health professionals.¹³ The results revealed that participants who consumed significantly more omega-6 than omega-3 fatty acid (intake ratio greater than 15:1) had an increased risk of dry eye compared to those who consumed a more balanced fatty acid intake (less than 4:1).

• Contact lenses. Contact lens wear is another significant risk factor for dry eye disease. Many studies have documented that more than 50% of current contact lens wearers complain of dry eye symptoms.¹⁴ Discomfort and dryness associated with contact lens wear continues to be the most common reason for patient dropout.¹⁵

Diagnostic Testing

Diagnostic testing allows you to examine and monitor the microenvironment of the ocular surface. Although there is no “gold standard” test used to identify dry eye, you still have a valuable armamentarium to help identify dry eye patients and to measure the success of therapy.

• Flourescein staining. One of the most valuable diagnostic tests is flourescein dye staining. Flourescein is a hydrophilic molecule best visualized under a cobalt blue light and a Tiffen #12 yellow filter (Tiffen Company).^16,17 Hold the Tiffen filter between the slit lamp and the patient to accentuate the presence or absence of flourescein dye.

Flourescein dye readily diffuses into the tear film and can be used to assess its integrity by measuring tear film break-up time (TFBUT). After applying flourescein onto the ocular surface, have the patient blink and then hold his or her eyes open. The time from the end of the blink to the appearance of the first dark area in the flourescein pattern is the TFBUT. Healthy patients generally demonstrate a TFBUT greater than 10 seconds.

The ocular protection index (OPI) describes how TFBUT relates to the time that the eye is open between blinks, or the interblink interval (IBI). An optimally protected ocular surface has a greater TFBUT than IBI.¹⁸

Flourescein can also be used to assess corneal integrity. Prolonged corneal insult secondary to dry eye can compromise tight junctions, which join neighboring epithelial cells. Additionally, localized depressions in the cornea may result from prolonged dryness to the ocular surface. Clinically, this finding appears as corneal staining.

Higher levels of fluorescein staining are seen with increased dry eye severity. Sometimes, however, there is a discrepancy between clinical signs of dry eye and the extent of patient symptoms. It is fairly common to see patients with significant corneal staining who demonstrate few symptoms. This may be due to an associated decrease in corneal sensitvity.^19,20 Interestingly, recent research indicated that patients who experience central corneal fluorescein staining after being exposed to a controlled adverse environment were more likely to have marked ocular discomfort scores.²¹

• Lissamine green and rose bengal staining. Lissamine green staining has recently garnered much interest from eye care providers who actively manage dry eye. This dye is similar to rose bengal because it detects dead and devitalized cells on the cornea and conjunctiva.¹⁶ Rose bengal, however, stings many dry eye patients upon instillation, while lissamine green does not. Lissamine green staining of the conjunctiva and/or cornea often reveals the presence of early dry eye.

The lid wiper represents the area on the posterior surface of the upper eyelid margin. This area is made up of squamous cells and has been shown to stain effectively with fluorescein, rose bengal and lissamine green dye in patients who exhibit dry eye symptoms. This staining is termed lid wiper epitheliopathy (LWE). In two separate studies, LWE was seen in 80% of contact lens patients with dry eye symptoms and 75% of non-contact lens patients with dry eye symptoms.^22,23

• Schirmer testing. Schirmer testing assesses aqueous production. A Schirmer score greater than 10mm within a five-minute period is considered normal. Schirmer testing can evaluate for basal tear secretion by instilling an anesthetic in the eye a few minutes before performing the test or reflex tearing by performing the test without anesthetic.

• Phenol red thread. A phenol red thread test is an alternative to Schirmer testing. Because a thread is used, there is significantly less patient awareness. Additionally, the thread needs to be in place for just 15 seconds. A reading greater than 10mm is considered normal.²⁴

Management Strategies

• Pharmaceutical education. Unfortunately, you usually do not have the liberty to alter or eliminate systemic medications that your patients are using. So, educate your patients about the potential side effects of pharmaceuticals that are more likely to cause ocular dryness.

• Environmental modifications. Small modifications in patients’ environments can potentially make a significant impact on tear film health. As mentioned above, extensive computer use, and therefore less blinking, places additional stress on the tear film. Further, a computer screen positioned directly at or above eye level exposes more of the ocular surface between blinks. So, instruct your patients to move their monitors below eye level to help reduce ocular surface stress.²⁵

Consumption of five to eight glasses of water per day is important for proper hydration.²⁶ Additionally, redirection of upward-facing forced air vents at work and home should help reduce dry eye symptoms. Finally, low humidity is very challenging for patients with dry eyes. Room humidifiers can help patients get through dry winters and arid climates. If that’s not enough, recommend moisture-chamber glasses/goggles that form a seal between the eyewear and the face to minimize tear evaporation.²⁷ Or, nighttime eyewear, such as Tranquileyes (EyeEco), can help retain moisture on the ocular surface.

• Contact lenses. Contact lenses can be used when a significant corneal staining is present. Soft contact lenses can be used as a bandage for some. For others who have more significant cornea compromise secondary to dry eye, a scleral contact lens may be warranted. This lens acts as a moisture chamber, rehabilitating those severely affected by dry eye disease.

• Artificial tears. Artificial tears have become a mainstay of dry eye therapy. They are generally regarded as first-line dry eye treatment. Usually, the success or failure of artificial tear therapy depends on several factors, including compliance with the recommended regimen and the type of artificial tear.

The cascade of dry eye disease can be a vicious cycle that begins with minor alterations to tear film integrity and the ocular surface. For many mild to moderate cases, regular use of artificial tears helps restore normal tear film and reduce symptoms. Unfortunately, however, many dry eye patients do not receive proper instructions on how to use artificial tears and only apply the drops when symptomatic. Sporadic dosing might alleviate symptoms temporarily, but does not help restore tear film health.

Another major challenge associated with artificial tear use is brand compliance. Consistent recommendation of the same artificial tear brand enhances patient compliance. Consider recommending a specific brand for a patient and then reinforcing the recommendation by providing him or her a sample, coupon or written prescription (or all three). This makes patient assessment at subsequent follow-up visits much more useful because you will be able to gauge the effectiveness of the selected drop.

When patients stray from your recommendations, it becomes more of a challenge to alleviate symptoms. Frequently, patients who discontinue use of the recommended brand opt for a lowercost store brand of artificial tears. The concern with some of these brands is that they may contain benzalkonium chloride (BAK). BAK can damage the ocular surface when dosed in a chronic fashion.^28-30 Unfortunately, BAK is also an issue for soft contact lens wearers because this preservative can be up-taken by the lens.

What is even more concerning with noncompliant patients is that they may select agents that contain vasoconstrictors. Vasoconstrictors have been shown to decrease tear volume and flow.³¹ Chronic use of these agents can result in a rebound hyperemic response.³² Another problem is that these drops also are preserved with BAK. So, be sure to make firm recommendations about the selection and use of artificial tears to maximize patient success.

• Lacrimal inserts. A novel way to deliver more lubrication to the ocular surface without use of an artificial tear is via lacrimal insert. Lacrimal inserts have been available for many years. They are 5mm in length and composed of hydroxypropyl cellulose. The insert is placed in the lower cul-de-sac, temporal to the cornea. The lacrimal insert slowly dissolves during a 24-hour period. As the implant dissolves, demulcent is released into the tear film.

The implant is inserted just once per day, as opposed to multiple times a day like an artificial tear. Consider this option for patients who reside in assisted living where others are responsible for administering multiple drops per day.

Recently, a large patient registry was performed using hydroxypropyl cellulose lacrimal inserts. During a one-month period, patients experienced an improvement in dry eye symptoms, frequency of symptom occurrence, discomfort experienced in various environmental conditions and the ability to perform activities of daily living.³³

• Proper nutrition and supplementation. Proper nutritional counseling can have a significant impact on ocular surface health. Omega-3 fatty acid supple mentation has become a staple treatment for dry eye patients. Omega-3 fatty acids have been shown to decrease inflammation, stimulate tear production and thin meibomian gland secretions.13,34,35 Instruct your dry eye patients to take 1,000mg to 2,000mg of omega-3 supplements per day. However, like most treatment options, the most important factor in effective omega-3 supplementation is patient compliance.

• Treatment of inflammation. Inflammation is directly associated with dry eye.^36,37 Eye care practitioners have widely embraced decreasing inflammation as part of a comprehensive dry eye treatment plan. Lotemax (loteprednol etabonate 0.5%, Bausch & Lomb) is a corticosteroid that has been widely embraced by the eye care community to control inflammation associated with dry eye disease.³⁸

Lotemax is usually dosed q.i.d. for a month before being tapered. Although infrequent, long-term corticosteroid use can increase IOP and cause formation of posterior subcapsular cataracts.³⁸

Restasis (cyclosporine 0.05%, Allergan) is the only FDA approved prescription medication for the treatment of dry eye. Restasis modulates T cells that play a critical role in aqueous deficient dry eye.³⁹ It is used b.i.d. and is packaged in sterile unit dose vials.

Restasis should be considered for dry eye patients who might benefit from long-term immunomodulation. Maximal efficacy of Restasis requires one to three months of therapy, and as such, some patients will begin concurrent therapy with loteprednol etabonate 0.5% during the first month of treatment.

• Treatment of the eyelids. The eyelids play an essential role in overall tear film health. The meibomian glands produce the tear film’s lipid layer. The meibomian glands are sebaceous glands located at the eye lid margin just posterior to the eye lashes.⁴⁰ Anything that affects meibomian gland function will reduce lipid flow and compromise tear film health.⁴¹ Expressing the glands of patients on examination will give the eye care practitioner a better sense of the fluidity of the lipids produced by the meibomian glands. Healthy meibomian glands will be easily expressed while those that are dysfunctional will be significantly more difficult to express.

Tear film lipids have been shown to have a melting point three degrees higher in patients with meibomian gland dysfunction (MGD) than healthy patients.⁴² So, direct heat with warm compresses is usually employed as a first-line therapy to remove coagulated oils in the meibomian glands.

If left untreated, however, meibomitis can cause gland pouting, lid margin tylosis and complete gland impairment.

The anti-inflammatory proper ties of oral tetracyclines often help treat MGD.^43-45 Oral doxycycline, the most commonly used tetra cycline for dry eye, typically is prescribed at 20mg to 100mg for one to three months, and is then tapered.

Recently, topical macrolides, such as azithromycin, have gained much attention in eye care by delivering both anti-bacterial and anti-inflammatory effects. Azithromycin 1% has been shown to decrease levels of matrix metalloproteinases and improve both signs and symptoms in patients with active MGD.⁴⁶

• Punctal plugs. Once you have reestablished tear film integrity, the next goal is to retain the tears on the eyes for a longer duration. This can be done with punctal plugs. Usually, the practitioner occludes the lower punctum initially, then the upper punctum, if needed. If punctal occlusion is performed prematurely, patients may feel less comfortable because they still have inflammatory mediators in the tear film.
• Autologous serum. Autologous serum may be an option for patients who still have significant issues with dry eye despite conventional therapy. In this case, a patient’s blood is drawn and the blood cells are separated from the plasma. The plasma is then combined with an artificial tear in sterile unit-dose vials. Finally, patients instill the drops two to four times a day. Several clinical studies confirm the value of autologous serum for severe dry eye patients.^47,48

As treatment options for dry eye continue to improve, we must stay abreast of current protocols and cutting-edge therapies. By understanding the risk factors and treatment options available, you can make a positive impact on your patients who suffer from dry eye disease.

Dr. Brujic is a partner of Premier Vision Group, a four location optometric practice in Northwest Ohio. He frequently lectures on contemporary topics in eye care. He has no financial interest in any of the products mentioned.

References

1. Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000 Sep;118(9):1264-8.
2. McCarty CA, Bansal AK, Livingston PM, et al. The epidemiol ogy of dry eye in Melbourne, Australia. Ophthalmology. 1998 Jun;105(6):1114-9.
3. Schein OD, Munoz B, Tielsch JM, et al. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997 Dec;124(6):723-8.
4. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003 Aug;136(2):318-26.
5. Gayton JL. Etiology, prevalence, and treatment of dry eye dis ease. Clin Ophthalmol. 2009;3:405-12.
6. Lemp MA, Baudouin C, Baum J, et al. The definition and clas sification of dry eye disease: Report of the Definition and Clas sification Subcommittee of the International Dry Eye Workshop (2007). Ocular Surf. 2007;75-92.
7. Abelson MB, Ousler GW 3rd, Maffei C. Dry eye in 2008. Curr Opin Ophthalmol. 2009 Jul;20(4):282-6.
8. Karpecki PM. Inflammation in dry eye disease. Contact Lens Spectrum. 2009 July. Available at: www.clspectrum.com/article. aspx?article=&loc=archive%5C2009%5Cjuly%5Ccls_july_a11. html (Accessed December 10, 2009).
9. Schlote T, Kadner G, Freudenthaler N. Marked reduction and distinct patterns of eye blinking in patients with moderately dry eyes during video display terminal use. Graefes Arch Clin Exp Ophthalmol. 2004 Apr;242(4):306-12.
10. Versura P, Campos EC. Menopause and dry eye. A possible relationship. Gynecol Endocrinol. 2005 May;20(5):289-98.
11. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001 Nov 7;286(17):2114-9.
12. Zylberberg C, Seamon V, Ponomareva O, et al. Estrogen up-regulation of metalloproteinase-2 and -9 expression in rabbit lacrimal glands. Exp Eye Res. 2007 May;84(5):960-72.
13. Miljanovi B, Trivedi KA, Dana MR, et al. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr. 2005 Oct;82(4):887-93.
14. Nichols JJ, Ziegler C, Mitchell GL, Nichols KK. Self-reported dry eye disease across refractive modalities. Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1911-4.
15. Pritchard N, Fonn D, Brazeau D. Discontinuation of contact lens wear: a survey. Int Contact Lens Clin. 1999 Nov;26(6):157-162.
16. Nichols JJ. Discovering dry eye: OSD management methods to dye for. Contact Lens Spectrum. 2005 May. Available at: www. clspectrum.com/article.aspx?article=12798 (Accessed December 10, 2009).
17. Abelson MB, Ingerman A. The dye-namics of dry eye diagno sis. Rev Ophth. 2005 Nov;12(11):72-5.
18. Emory TB, Ousler 3rd GW, Abelson MB. All in the blink of an eye. Rev Ophth. 2002 Mar;9(3):82-5.
19. Xu KP, Yagi Y, Tsubota K. Decrease in corneal sensitivity and change in tear function in dry eye. Cornea. 1996 May;15(3):235 9.
20. Bourcier T, Acosta MC, Borderie V, et al. Decreased corneal sensitivity in patients with dry eye. Invest Ophthalmol Vis Sci. 2005 July;46(7):2341-5.
21. Ousler GW. An association between central corneal staining and dry eye symptomolagy. Poster presented at the 2006 Associa- tion for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 30-May 4; Fort Lauderdale, Fla.
22. Korb DR, Greiner JV, Herman JP, et al. Lid-wiper epitheliopa thy and dry-eye symptoms in contact lens wearers. CLAO J. 2002 Oct;28(4):211-6.
23. Korb DR, Herman JP, Greiner JV, et al. Lid wiper epitheliopa thy and dry eye symptoms. Eye Contact Lens. 2005 Jan;31(1):2-8.
24. Vorvick L, Zieve D. Merck Source. Schirmer’s Test. Available at: www.mercksource.com/pp/us/cns/cns_hl_adam.jspzQzp gzEzzSzppdocszSzuszSzcnszSzcontentzSzadamfullzSzadam_ encyzSz1zSz003501zPzhtm (Accessed Dec 10, 2009).
25. Kanitkar K, Carlson AN, Yee R. Ocular problems associated with computer use. Rev Ophth. 2005 Apr;12(4):47-52.
26. Snyder C. All dryness in contact lens wear. Contact Lens Spectrum. 1998 August. Available at: www.clspectrum.com/ article.aspx?article=&loc=archive%5C1998%5Caugust% 5C0898035.htm (Accessed on December 10, 2009).
27. Hart DE, Simko M, Harris E. How to produce moisture cham ber eyeglasses for the dry eye patient. J Am Optom Assoc. 1994 Jul;65(7):517-22.
28. López Bernal D, Ubels JL. Quantitative evaluation of the cor neal epithelial barrier: effect of artificial tears and preservatives. Curr Eye Res. 1991 Jul;10(7):645-56.
29. Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008 Nov;86(7):716-26.
30. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocu lar surface disease in glaucoma patients. J Glaucoma. 2008 Aug;17(5):350-5.
31. Göbbels MJ, Achten C, Spitznas M. Effect of topically applied oxymetazoline on tear volume and tear flow in humans. Graefes Arch Clin Exp Ophthalmol. 1991;229(2):147-9.
32. Bielory L, Lien KW, Bigelsen S. Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis. Drugs. 2005;65(2):215-28.
33. Koffler BH. Lacrisert (hydroxypropylcellulose ophthalmic inserts) significantly improves symptoms of dry eye syndrome (DES) and patient quality of life. Poster presented at the 2009 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, May 3-7; Ft. Lauderdale, Fla.
34. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000 Jan;71(1 Suppl):343S-8S.
35. Sullivan RM. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjögren’s Syndrome. Lecture presented at the Third Inter national Conference on the Lacirmal Gland, Tear Film and Dry Eye Syndromes: Basic Science and Clinical Relevance 2000. November 15-18 in Maui, Hawaii.
36. Jackson WB. Management of dysfunctional tear syndrome: a Canadian consensus. Can J Ophthalmol. 2009 Aug;44(4):385 94.
37. Latkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol. 2008 Jul;19(4):287-91.
38. Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9.
39. Allergan. Restasis package insert. 2009.
40. Hart WM. Adler’s Physiology of the Eye, 9th ed. Philadel phia: Mosby Yearbook, 1992:19-24.
41. Joffre C, Souchier M, Grégoire S, et al. Differences in mei bomian fatty acid composition in patients with meibomian gland dysfunction and aqueous-deficient dry eye. Br J Ophthalmol. 2008 Jan;92(1):116-9.
42. Ong BL, Larke JR. Meibomian gland dysfunction: some clinical, biochemical and physical observations. Ophthalmic Physiol Opt. 1990 Apr;10(2):144-8.
43. De Paiva CS, Corrales RM, Villarreal AL, et al. Corticoste roid and doxycycline suppress MMP-9 and inflammatory cyto kine expression, MAPK activation in the corneal epithelium in experimental dry eye. Exp Eye Res. 2006 Sep;83(3):526-35.
44. Aronowicz JD, Shine WE, Oral D, et al. Short term oral minocycline treatment of meibomianitis. Br J Ophthalmol. 2006 Jul;90(7):856-60.
45. Jacot J. Evaluation of MMP2/9 modulation by azithromycin and Durasite on human corneal epithelial cells and bovine corneal endothelial cells in vitro. Poster presented at the 2008 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 27-May 1; Ft. Lauderdale, Fla.
46. Foulks GN, Borchman D, Yappert CM. Modification of meibomian gland lipids by azithromycin. Poster presented at the 2006 Association for Research in Vision and Ophthalmol ogy (ARVO) Annual Meeting, April 30-May 4; Fort Lauderdale, Fla.
47. Kojima T, Higuchi A, Goto E, et al. Autologous serum eye drops for the treatment of dry eye diseases. Cornea. 2008 Sep;27 Suppl 1:S25-30.
48. Kojima T, Ishida R, Dogru M, et al. The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case-control study. Am J Ophthalmol. 2005 Feb;139(2):242-6.