The Importance of the Ocular Surface in the Surgical Patient

Richard Lindstrom, MD

Trauma from ocular surgery can result in inflammation, so ideally surgery should only be performed on an eye free from pre-existing inflammation. Furthermore, infection can occur as a result of surgery. There is a higher colony count of pathogens that commonly cause endophthalmitis when a patient has dry eye syndrome and/or blepharitis. Therefore, when a patient first presents for surgery, special attention should be given to the ocular surface, specifically the diagnosis and treatment of dry eye syndrome and blepharitis. Diagnosing and treating these conditions preoperatively decreases the risk of postoperative infection and inflammation, improving surgical outcomes—both quality of vision and rate of patient recovery. When these conditions are ignored preoperatively, patients are less likely to be satisfied with the outcomes of surgery. Protecting the eye during surgery is another important aspect of reducing postoperative infection and inflammation. Postoperative maintenance is also crucial in the prevention of postoperative infection and inflammation. These issues will be discussed later in this monograph.

Preoperative Evaluation

Dry eye syndrome and blepharitis can both be diagnosed by history and thorough external ocular examination. Many patients are diagnosed with dry eye syndrome when they come to the ophthalmologist for surgery. Moreover, while 78% of patients with blepharitis present to the ophthalmologist because of either symptoms of dry eye syndrome or blepharitis, 16% of patients are diagnosed upon surgical evaluation.¹ Thus, a thorough history and physical examination of the ocular surface should be performed for every ocular surgical patient.

Diagnosis of posterior blepharitis

In the diagnosis of posterior blepharitis, lid function should be assessed by counting the blink rate and checking for lagophthalmos (the ability to completely close the eyelids). The posterior lid margin should be inspected for evidence of meibomian gland dysfunction—inspissation of glands, erythema, telangiectasia, pouting of oil, and gland drop out—all of which increase the risk of postoperative complications. Minor pressure on the lower lid, applied with either with a finger or a cotton swab, may produce significant meibomian gland expression of abnormal secretions. The tear film volume quality and quantity should be evaluated through examination of the tear lake at the lid margin. Foamy tears or debris in the tear meniscus are pathognomonic of meibomian gland dysfunction. Meibomian gland dysfunction can lead to dry eye syndrome secondary to an unstable tear film.

Diagnosis of dry eye syndrome

Currently, dry eye syndrome is diagnosed through examination of conjunctival epithelium with surface staining using either rose bengal or lissamine green. Examination of tear break-up time and the lid margin tear film to assess the size of the tear meniscus can also be useful. The Schirmer test is useful in assessment of patients with a condition like Sjögren’s syndrome.² An instrument that measures tear osmolarity is under development that may be useful for diagnosing dry eye syndrome in the future.

All preoperative patients should have their conjunctival epithelium examined before conjunctival staining. Often a surgeon will only see patients after they have fluorescein in their eye and a technician has measured IOP with a tonometer. Examining where the tonometer was set against the cornea can serve as an “ocular surface stress test.” A large amount of punctate staining and the visibility of the arc of the tonometer on the corneal epithelium indicate that an eye has a relatively low reserve for trauma as far as the ocular surface is concerned. When the lissamine green is added, staining is often present on the conjunctiva as well as the cornea.

Dry Eye Syndrome

Dry eye syndrome is a chronic condition associated with advanced age, hormonal deficiencies, the use of anticholinergic agents, surgery, systemic autoimmune disease, computer use, and environmental factors. Elevated tear film osmolarity is a key marker of dry eye syndrome. Dry eye syndrome comprises a group of disorders of the tear film due to reduced tear production, excessive tear evaporation, and/or inadequate tear spreading. Inflammation has recently been recognized as a key component in dry eye syndrome, rendering anti-inflammatory agents useful in the treatment of this condition.

Prevalence

The prevalence of dry eye syndrome varies from 7.4% to 33.7% worldwide. The Beaver Dam population study found that 14.4% of adults aged 48 to 91 years had dry eye syndrome. The prevalence was higher in females (16.7%) than in males (11.4%). As in other studies, the prevalence in both genders increased with age.³

In the Women’s Health Study, 39,876 US women were surveyed about dry eye syndrome and its symptoms.⁴Among women younger than 50, the prevalence of dry eye syndrome was 5.7%, while the prevalence of dry eye syndrome in women aged 75 years and older was 9.8%. The study concluded that the age-adjusted prevalence of dry eye syndrome was 7.8% in women aged 50 years and older, meaning 3.23 million women aged 50 years and older are affected in the United States.

The Physicians’ Health Studies I and II included 25,444 men aged 55 years and older. In this population of physicians, 4.3% reported having a clinical diagnosis or severe symptoms of dry eye syndrome.⁵ As in the Women’s Health Study, men aged 75 years and older were more likely to have dry eye syndrome. The observed prevalence rose from 3.9% among men aged 50 to 54 years to 7.7% among men aged 80 years and older (P for trend < .0001).

Diagnosis and Treatment of Dry Eye Syndrome

The Delphi Panel was convened by the Dry Eye International Task Force to reach a consensus on the diagnostic parameters of dry eye syndrome (Table 1).⁶ There are 4 diagnostic levels of severity identified and recommendations for treatment were made. Level 1 treatment focuses mainly on patient education and conservative management. At level 2, characterized by moderate to severe symptoms and minimal clinical signs, topical steroids and cyclosporine are recommended to effectively and rapidly control inflammation and to obtain a more favorable outcome. Artificial tears, gels, ointments, secretagogues, and nutritional supplements are also recommended at level 2.

Table 1. Dry Eye Syndrome Diagnosis and Treatment

*Corticosteroid use is off-label for dry eye syndrome.
Source: Behrens A, et al. Cornea. 2006;25:900-907.

Click here for a larger view of this image.

The American Academy of Ophthalmology (AAO) has also established preferred practice patterns for dry eye syndrome.⁷Severity varies and patients may not fit into the categories precisely. The AAO recommends that for mild dry eye syndrome, management should include patient education, environmental modifications, elimination of offending systemic or topical medications, aqueous enhancement (ie, artificial substitutes, gels/ointments), eyelid therapy, and treatment of contributing ocular factors. Management for moderate dry eye syndrome should include (in addition to treatments for mild dry eye syndrome) topical anti-inflammatory agents, systemic omega-3 fatty acid supplements, punctal plugs, and systemic side shields and moisture chambers. For severe dry eye syndrome, additional measures must be implemented, including systemic cholinergic agonists, systemic anti-inflammatory agents, mucolytic agents, autologous serum tears, contact lenses, correction of eyelid abnormalities, permanent punctal occlusion, and tarsorrhaphy.

Ocular surface disease is common in the cataract patient and ocular surgery increases the severity of ocular surface disease by 1 to 2 levels.⁶ Therefore, dry eye syndrome should be treated before surgery is performed. Like any other condition involving inflammation of the eye, dry eye syndrome should be treated aggressively to eliminate the inflammation. Steroids are potent anti-inflammatory agents and have proven effective in both evaporative and aqueous deficient dry eye syndrome.⁸

Corticosteroids do, however, carry risks. They can lead to ocular hypertension, cataract formation, diminished wound healing, and an increased risk of secondary infection. To minimize the risk of these complications, soft steroids such as loteprednol can be used. Loteprednol has an improved safety profile when compared to ketone corticosteroids like dexamethasone and prednisolone.^9-12For example, in a study comparing the incidence of clinically significant IOP elevations (> 10 mm Hg) associated with loteprednol and prednisolone acetate, the incidence of IOP elevations was 0.5% with vehicle, 1.7% with loteprednol, and 6.7% with prednisolone.¹⁰

Cyclosporine continues to be an important tool for treating dry eye syndrome. Multiple studies have shown that topical cyclosporine improves multiple aspects of ocular surface diseases—tear production, corneal staining, visual acuity, and meibomian gland function.^6,13,14 There are, however, limitations associated with cyclosporine. Cyclosporine can take up to 3 to 4 months to reach maximum efficacy, and 17% of patients have burning symptoms at onset of treatment.^13,15Combining a course of topical steroids with cyclosporine minimizes this discomfort and decreases the time from the onset of treatment to elimination of corneal staining.

Loteprednol etabonate 0.5% in combination with cyclosporine provides rapid relief of dry eye syndrome signs and symptoms with greater efficacy than cyclosporine and artificial tears alone. This is evidenced by greater improvement in corneal and conjunctival staining, improvement in the Schirmer test, reduction in the frequency of adjunctive artificial tear use, and reduction of Ocular Surface Disease Index scores. Long-term treatment (60 days) with loteprednol did not affect IOP.¹⁶ Treatment with combined 0.05% cyclosporine solution and 1% methylprednisolone has also been proven more effective than treatment with cyclosporine alone in a study of 44 patients with moderate to severe dry eye syndrome who had not responded to conventional treatment.¹⁷

The Aesclepius panel developed a treatment regimen for dry eye syndrome with the primary objectives being to address the role of inflammation in dry eye syndrome and to provide a recommended corticosteroid dose and formulation (Figure 1).^18,19 The treatment model involves the use of soft steroids, cyclosporine, and artificial tears. According to these recommendations, treatment is initiated with soft steroid eye drops 4 times per day with artificial tears implemented as needed. After 2 weeks, cyclosporine drops are added 2 times per day while the steroids are tapered to 2 times per day. This regimen is implemented until day 60, after which steroid use is stopped and the patient then remains on cyclosporine drops twice per day for life. Soft steroids can be restarted for any breakthrough inflammatory reactions. Artificial tears can also be used throughout the regimen.

As discussed previously, there are also treatment options for severe dry eye syndrome, such as punctal plugs.^6,20 Punctal plugs must be utilized after inflammation is controlled to prevent retention of inflammatory mediators. Low-dose oral doxycycline (20 mg once per day or 50 mg every day) and autologous serum drops may also be effective.

Figure 1. Recommended Treatment Model for Dry Eye Inflammation

Combining a course of topical steroids with cyclosporine minimizes the discomfort associated with cyclosporine and decreases the time from the onset of treatment to elimination of corneal staining.
Source: Holland EJ. Ophthalmol Times. 2007;32:3-11

Click here for a larger view of this image.

Blepharitis

The cataract patient with dry eye syndrome often has blepharitis as well. The US military found that 5% of recruits and 71% of retirees have blepharitis.²¹ This study highlights the observation that the prevalence of blepharitis increases with age. A telephone survey of 120 ophthalmologists revealed that in these practices 37% of patients have blepharitis.¹

Blepharitis should be treated before any ocular surgery. Antibiotics to reduce the bacterial count and steroids to alleviate inflammation are recommended. Combinations of tobramycin and loteprednol and tobramycin and dexamethasone are available and improve the quality of meibomian gland secretions.^22-24Azithromycin is another option; this agent has a broad spectrum of antibiotic activity and anti-inflammatory activity without the side effects of steroids.^25-27 This antibiotic also has a high ability to penetrate ocular tissues, including the conjunctiva and eyelids, to achieve effective and sustained levels. Azithromycin, however, takes approximately 4 weeks to achieve maximum results. Combining a steroid with azithromycin is a reasonable option.

Other options for treatment of blepharitis include medicated lid scrubs and lid hyperthermia through hot compresses or mechanical devices. Nutritional supplements are also helpful. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) thin meibomian gland secretions and are also useful in the treatment of dry eye syndrome. Fish oil and flaxseed oil have both been proven effective.^14,28-30 Eicosapentaenoic and docosapentaenoic polyunsaturated fatty acids reduce inflammation.

Surgery in the Patient with Ocular Surface Disease

Surgery should be avoided if there are significant signs and symptoms of dry eye syndrome and blepharitis (Table 2). Patients cannot always become symptom-free, but if staining and signs are gone, surgery can be performed. Importantly, management does not end with surgery. Antibiotics and steroids should also be implemented for 1 to 2 weeks postoperatively to further reduce the risk of infection and inflammation. These measures will lead to improved outcomes and patient satisfaction.

Table 2. When to Avoid Surgery Due to Ocular Surface Disease

Source: Richard L. Lindstrom, MD

Click here for a larger view of this image.

References

Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009;7(2 suppl):S1-S14.
Whitcher JP, Shiboski CH, Shiboski SC, et al; Sjögren’s International Collaborative Clinical Alliance Research Groups. Am J Ophthalmol. 2010;149(3):405-415.
Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000;118(9):1264-1268.
Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136(2):318-326.
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):763-768.
Behrens A, Doyle JJ, Stern L, et al; Dysfunctional tear syndrome study group. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25(8):900-907.
American Academy of Ophthalmology. Preferred Practice Pattern. Dry Eye Syndrome. http://one.aao.org/CE/PracticeGuidelines/PPP.aspx?sid=9955f101-a94b-4f8f-a3c9-15d014f613b9. Accessed February 1, 2011.
Pflugfelder SC, Maskin SL, Anderson B, et al. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138(3):444-457.
Howes J, Novack GD. Failure to detect systemic levels, and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration. J Ocul Pharmacol Ther. 1998;14(2):153-158.
Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998;7(4):266-269.
Howes JF. Loteprednol etabonate: a review of ophthalmic clinical studies. Pharmazie. 2000;55(3):178-183.
Holland EJ. Steroid selection in dry eye: why loteprednol etabonate? Refract Eyecare. 2005;9(suppl):17-19.
Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmol. 2000;107(4):631-639.
Ambrósio R Jr, Tervo T, Wilson SE. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. J Refract Surg. 2008;24(4):396-407.
Restasis (cyclosporine ophthalmic emulsion 0.05%) prescribing information. Irvine, CA: Allergan, Inc; 2004.
Donnenfeld E, Holland EJ, Lane SS, et al. Prospective, multicenter, randomized controlled study on the effect of loteprednol etabonate on initiating therapy with cyclosporine A. Presented at: American Academy of Ophthalmology 2007 Annual Meeting; November 10-13, 2007; New Orleans, LA.
Byun YJ, Kim TI, Kwon SM, et al. Efficacy of combined 0.05% cyclosporine and 1% methylprednisolone treatment for chronic dry eye [published online ahead of print August 31, 2009]. Cornea. http://www.ncbi.nlm.nih.gov/pubmed/19730097. Accessed March 7, 2011.
McDonald MB. The inflammatory etiology of dry eye. Refract Eyecare. 2005;9:3-6.
Holland EJ, Donnenfeld ED, Lindstrom RL, Pflugfelder SC, Sheppard JD, Solomon KD. Expert consensus in the treatment of dry eye inflammation. Based on the proceedings of a symposium held during the 2006 American Academy of Ophthalmology Joint Meeting. Ophthalmol Times. 2007;32(suppl 7):3-11.
Donnenfeld ED. Minimizing post-LASIK dry eye. Aggressive preoperative and intraoperative management will reduce the incidence of this complication. Ophthalmology Management. 2004. http://www.ophmanagement.com/article.aspx?article=86170. Accessed January 11, 2008.
Stanek S. Meibomian gland status comparison between active duty personnel and US veterans. Mil Med. 2000;165(8):591-593.
Rhee SS, Mah FS. Comparison of tobramycin 0.3%/dexamethasone 0.1% and tobramycin 0.3%/loteprednol 0.5% in the management of blepharo-keratoconjunctivitis. Adv Ther. 2007;24(1):60-67.
Bartlett JD, Holland EJ, Usner DW, Paterno MR, Comstock TL. Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-week, randomized, double-masked, parallel-group study. Curr Med Res Opin. 2008;24(8):2219-2227.
White EM, Macy JI, Bateman KM, Comstock TL. Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis. Curr Med Res Opin. 2008;24(1):287-296.
Saiman L, Marshall BC, Mayer-Hamblett N, et al; Macrolide Study Group. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003;290(13):1749-1756.
John T, Shah AA. Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis. Ann Ophthalmol (Skokie). 2008;40(2):68-74.
Luchs J. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. Adv Ther. 2008;25(9):858-870.
Schwab IR. Presented at: Ocular Microbiology and Immunology Group Annual Meeting; 1990.
Brown NA, Bron AJ, Harding JJ, Dewar HM. Nutrition supplements and the eye. Eye. 1998;12(pt 1):127-133.
Sullivan BD, Cermak JM, Sullivan RM, et al. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjögren's syndrome. Adv Exp Med Biol. 2002;506(pt A):441-447.