Reducing Postoperative Ocular Infection and Inflammation

Dry eye disease (DED) describes a group of disorders of the tear film caused by reduced tear production, excessive tear evaporation, or inadequate tear spreading. Anterior segment surgery, particularly cataract surgery and LASIK, can increase the risk of chronic postoperative DED by altering ocular surface and tear-film dynamics. Surgery on a patient with significant DED or blepharitis can also increase the risk of postoperative infection and blepharitis, which in turn can exacerbate DED. However, with careful preoperative, intraoperative and postoperative management, clinicians can reduce the incidence and severity of chronic dry eye in patients undergoing ocular surgery.

Burden of Postsurgical Disease

Worldwide, dry eye affects 7.4% to 33.7% of the population.¹Estimates of the prevalence of DED in the United States vary across studies. In the Beaver Dam Eye Study, the overall prevalence was 14.4% in adults ages 48 to 91 years.² However, prevalence of the disease increased significantly with age, from 8.4% in adults younger than 60 to 19% in those older than 80 (p < .001). With data adjusted for age, DED also occurred with greater frequency among women than men (16.7% versus 11.4%, respectively; p < .001).² In the Women’s Health Study, prevalence increased from 5.7% among women younger than 50 to 9.8% among those 75 or older.³ The overall prevalence was 7.8%, suggesting that DED affects 3.23 million U.S. women ages 50 years or older.³

Inflammation is increasingly recognized as a pathological component of idiopathic and postsurgical DED. DED is associated with infiltration of lymphocytes into conjunctival tissues and immune-mediated inflammation of lacrimal glands and ocular surface. Inflammation disrupts the normal neuronal control of tearing, leading to cytokines in tears and altered tear composition. The process has multiple triggers and predisposing factors.

Blepharitis is an inflammatory disease of the eyelid with abnormal eyelid flora as the primary etiologic determinant. The condition, which may cause or contribute to DED, is commonly seen in practice.⁴ According to a survey of ophthalmologists, 37% of patients in their practices had blepharitis.⁵ Of these patients, however, only 35% sought evaluation for blepharitis symptoms. Most patients with blepharitis were diagnosed as the result of evaluation for DED (43%), surgical evaluation (16%) or routine examination (6%).⁵ In a study of U.S. Military personnel, blepharitis was observed in 4.7% of active duty service members and 71.1% of retirees, reflecting the increased prevalence of blepharitis with age.⁶

Anterior segment surgery may contribute to postoperative chronic DED. In 2007, the International Dry Eye Workshop (DEWS) defined 4 categories of dry eye severity: mild to moderate, moderate to severe, severe, and extremely severe (Table 1).⁴ Different types of anterior segment surgery can affect the severity of dry eye symptoms. Without aggressive ocular surface preparation and protection, cataract surgery can add one severity level (e.g., shift mild to moderate disease to moderate to severe disease), and LASIK can add two.

Table 1. Dry Eye Workshop (DEWS): Diagnosis and Treatment Recommendations

*Corticosteroid use is off-label for dry eye disease.
The International Dry Eye Workshop (DEWS) defined 4 categories of dry eye severity.
Source: Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25:900-907.

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Surgical Planning

In most cases, surgery should be avoided when significant signs and symptoms of ocular surface disease persist (Table 2). To prevent endophthalmitis, patients should receive preoperative treatment for blepharitis and DED. During surgery, use of sterile technique, povidone-iodine preparation, careful lid draping, epithelium protection, and careful wound construction can further reduce the risk of postoperative complications.

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

In most cases, surgery should be avoided when significant signs and symptoms of ocular surface disease persist.
Source: Richard L. Lindstrom, MD

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Anti-inflammatory Agents

Corticosteroids improve tear production in patients with DED by controlling inflammation on the ocular surface.⁷ Treatment with anti-inflammatory agents, including corticosteroids, cyclosporine and doxycycline, counteracts the effects of reduced tear secretion, decreased tear turnover and desiccation on the ocular surface. In patients with DED, anti-inflammatory therapy enhances aqueous tear production, reduces blurred vision, decreases corneal punctuate fluorescein staining and decreases artificial tear use.⁷

Topical Steroids

Topical corticosteroids improve multiple objective and subjective measures of dry eye and ocular surface disease, including tear production, corneal staining, visual acuity and meibomian gland function.⁴The limitations of corticosteroid therapy in the long-term treatment of DED include risk of ocular hypertension, cataract formation, diminished wound healing effects and increased risk of secondary infection.⁷

Cyclosporine A

Two phase III multicenter randomized studies evaluated cyclosporine A (CsA) 0.05% and 0.1% ophthalmic emulsion in 877 patients with moderate to severe DED.⁸ Compared with placebo, treatment with twice daily CsA 0.05% or 0.1% significantly improved response as measured by corneal staining and Schirmer values, with no evidence of toxicity. The CsA 0.05% preparation also significantly improved visual acuity, reduced the need for artificial tears and improved global response to treatment compared with placebo.⁸ These findings underscore the benefits of topical therapy in patients with moderate to severe DED.

Topical CsA is a reasonable option for patients needing long-term maintenance, but it may not be appropriate for patients who require more immediate relief. The clinical benefits of topical CsA are delayed, requiring up to 3 to 4 months of treatment to achieve maximal efficacy.^7,9 Furthermore, approximately 17% of patients treated with topical CsA emulsion report discomfort during treatment.⁹ Increased irritation, even over the short-term, may be a deterrent to long-term use.⁹

Combination Therapy

Given the limitations of standard treatment with topical CsA ophthalmic emulsion, several investigators have explored options for improving the standard of care in patients with DED. In 2007, the Asclepius Panel recommended a combination regimen for managing inflammation associated with dry eye.¹⁰ The 60-day regimen, which could be continued indefinitely, included the following:

Artificial tears days 1 to 60
Soft steroids day 1 to 60

4 times daily days 1 to 15
Twice daily days 15 to 60,
switching to 4 times daily as need for flare-ups

Cyclosporine twice daily from days 15 to 60

In a prospective, multicenter, randomized study, investigators evaluated the use of loteprednol etabonate 0.5% in patients who planned to initiate treatment with topical CsA. The 118 patients with clinically diagnosed DED were randomly assigned to treatment with loteprednol etabonate 0.5% or artificial tears (vehicle) 4 times daily for 2 weeks. At day 15, all patients began treatment with topical CsA and continued through day 60, with additional use of artificial tears allowed as needed. By day 60, combination therapy with loteprednol etabonate 0.5% and CsA relieved the signs and symptoms of dry eye with greater efficacy than CsA and artificial tears alone, as 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 in Ocular Surface Disease Index scores. Long-term loteprednol etabonate 0.5% did not adversely affect intraocular pressure.¹¹

Combination therapy with CsA 0.05% and 1% methylprednisolone is also an effective treatment regimen for patients with DED. Researchers evaluated this combination in a study of 44 patients with moderate to severe chronic DED who had not responded to conventional therapy.¹² Patients were randomly assigned to treatment with 1% methylprednisolone and topical CsA for 3 weeks followed by single-agent CsA thereafter (n=21) or topical CsA only for the duration of treatment (n=23). Short-term use of 1% methylprednisolone provided faster symptom relief and greater improvement in ocular signs of DED, without serious complications. After 1 month, the combination group showed greater improvements in symptom scores (p < .001), Schirmer scores (p = 0.039) and corneal staining (p = .01) compared with the CsA monotherapy group. By 3 months, patients in both groups showed decreased tear IL-6 and IL-8 concentrations compared with baseline levels (p < .05), with no differences between treatment groups.¹²

For patients with severe DED, punctal plugs are an option, but only after inflammation and lid disease are controlled to prevent retention of inflammatory cytokines. Oral doxycycline is another treatment option, particularly as low-dose therapy (50 mg daily or 20 mg twice a day). Autologous serum drops can also be used to address the symptoms of severe DED.^4,13

Treatment of Blepharitis

Patients with postoperative chronic DED may also have blepharitis. Treatments for blepharitis include lid hyperthermia with hot compresses and mechanical devices, medicated lid scrubs and nutritional supplements.^4,17 As an option for topical therapy, topical antibiotic ophthalmic preparations can penetrate ocular tissue, including the conjunctiva and eyelid, to achieve effective and sustained levels of anti-inflammatory activity. Topical antibiotics with broad-spectrum antimicrobial activity can also quickly improve the quality of meibomian gland secretions. Alone and in combination with warm compresses, topical azithromycin ophthalmic solution 1% is associated with rapid relief of several clinical signs of blepharitis, including meibomian gland plugging and secretions, and eyelid redness.^18,19

Topical antibiotic/steroid combinations are also effective in the patients with moderate to severe blepharitis. Loteprednol etabonate ophthalmic 0.5% suspension is a topical corticosteroid that shows modest improvements in the signs of inflammation in patients with DED.²⁰ In a multicenter, randomized trial, treatment with tobramycin 0.3%/dexamethasone 0.1% provided greater improvements in the signs of ocular inflammation, including blepharitis, discharge and conjunctivitis, compared with treatment with tobramycin 0.3% / loteprednol 0.5% in patients with blepharokeratoconjunctivitis.²¹ In another trial, tobramycin 0.3%/lote
prednol 0.5% was similar to tobramycin 0.3%/dexamethasone 0.1% in terms of overall comfort and tolerability, but showed greater improvement from baseline in individual ratings of pain, stinging, burning, irritation, itchiness, foreign-body sensation and light sensitivity.²² Some investigators have also observed an increased intraocular pressure in patients treated with tobramycin 0.3%/dexamethasone 0.1%.²³

Summary

Patients undergoing anterior segment surgery are at risk for developing inflammation and infection of the ocular surface, resulting in chronic DED, blepharitis and other complications that can affect visual outcomes. Topical corticosteroids are effective anti-inflammatory agents that can relieve the signs and symptoms of moderate or severe DED. Combination regimens that incorporate topical antibiotics are also effective in minimizing the signs and symptoms of blepharitis. Careful surgical planning and management can reduce the risk and severity of postoperative inflammation and infection. n

References

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